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Petes, Thomas Douglas

Overview:

My lab is active in three somewhat related research areas: 1) the mechanism of mitotic recombination, 2) the genetic regulation of genome stability, and 3) genetic instability associated with interstitial telomeric sequences. Almost all of our studies are done using the yeast Saccharomyces cerevisiae.


Mechanism of mitotic recombination


Mitotic recombination, an important mechanism for the repair of DNA damage, is less well characterized than meiotic recombination. One difficulty is that mitotic recombination events are 104-fold less frequent than meiotic recombination events. We developed a greatly improved system for identifying and mapping mitotic crossovers at 1-kb resolution throughout the genome. This system uses DNA microarrays to detect loss of heterozygosity (LOH) resulting from mitotic crossovers. We identified motifs associated with high levels of spontaneous mitotic recombination. In particular, we demonstrated that a “hotspot” for mitotic recombination was generated by a pair of inverted retrotransposons. We also used this system to make the first genome-wide map of UV-induced recombination events. Finally, and most importantly, we demonstrated that most spontaneous mitotic recombination events reflect the repair of two sister-chromatids broken at the same position. This result argues that the DNA lesions that initiate mitotic recombination are a consequence of chromosome breakage in unreplicated DNA, contrary to the common belief that most recombinogenic lesions reflect broken replication forks. We are currently analyzing recombination events that occur in the absence of DNA mismatch repair.


Genetic regulation of genome stability


In wild-type cells, the frequency of genomic alterations of any type (point mutations, deletions, insertions, and chromosome rearrangements) is very low. We are interested in the genes that regulate genome stability. One rationale for this interest is that the cells of most solid tumors have very high levels of chromosome rearrangements (deletions, duplications, and translocations) as well as high levels of aneuploidy. To understand this type of instability, we are examining the chromosome instability associated with various genome-destabilizing conditions in yeast. We are currently concentrating on mutations that affect DNA replication. We have mapped chromosome rearrangements in yeast strains with low levels of DNA polymerase alpha. This mapping indicated that DNA breaks occur in regions of the genome in which replication forks are slowed or stalled. This pattern of recombination events is quite different from that observed in cells with normal replication. In collaboration with Sue Jinks-Robertson’s lab, we have also characterized chromosome alterations in strains with mutations in Topoisomerase I and cells treated with Topoisomerase I inhibitors. Our analysis is currently being extended into strains with mutations affecting Topoisomerase II, and mutations in DNA damage repair checkpoint genes. Our preliminary study shows that loss of Topoisomerase II results in an interesting pattern of chromosome non-disjunction in which chromosomes segregate in a manner similar to the first division of meiosis.


Genetic regulation of genome stability


Although telomeric sequences are usually located at the ends of the chromosome, mammalian chromosomes also have interstitial telomeric repeats (ITSs), and these ITSs are often sites of chromosome rearrangements in tumor cells. In collaboration with Sergei Mirkin’s lab, we developed methods of detecting ITS-induced genome instability in yeast. We are currently examining the effects of mutations in recombination (RAD52, RAD51, MUS81, RAD50, MRE11, LIG4, RAD59), DNA repair (RAD1, MSH2), DNA replication (REV3), and telomere length maintenance (TEL1, RIF1) pathways on the rates and types of ITS-induced events. The goal of this project is to identify the proteins required to initiate DNA lesions at ITSs and the proteins required to catalyze the ITS-associated rearrangements.

Positions:

Minnie Geller Professor of Research in Genetics, in the School of Medicine

Molecular Genetics and Microbiology
School of Medicine

Professor of Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1973

Ph.D. — University of Washington

News:

Grants:

Genetic regulation of genome stability in yeast

Administered By
Molecular Genetics and Microbiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 2016
End Date
June 30, 2021

Molecular Mycology and Pathogenesis Training Program

Administered By
Molecular Genetics and Microbiology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
August 08, 2014
End Date
July 31, 2019

Generation of genomic duplications and deletions in yeast

Administered By
Molecular Genetics and Microbiology
AwardedBy
Army Research Office
Role
Principal Investigator
Start Date
June 15, 2015
End Date
March 31, 2019

Genetic regulation of genome stability in yeast

Administered By
Molecular Genetics and Microbiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
May 01, 2005
End Date
September 30, 2016

Recombination in yeast

Administered By
Molecular Genetics and Microbiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
March 01, 2005
End Date
June 30, 2016

Topoisomerase-Associated Genome Instability

Administered By
Molecular Genetics and Microbiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 2012
End Date
June 30, 2014

Mechanisms of Centromere Function

Administered By
Molecular Genetics and Microbiology
AwardedBy
National Institutes of Health
Role
Co-Sponsor
Start Date
August 11, 2010
End Date
August 10, 2013

Environmental and genetic regulation of copy number variation (CNV)

Administered By
Molecular Genetics and Microbiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 26, 2009
End Date
June 30, 2011

Characterization of Chromosome Fragile Sites in Yeast

Administered By
Molecular Genetics and Microbiology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 01, 2006
End Date
June 30, 2006
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Awards:

The Thomas Hunt Morgan Medal. Genetics Society of America.

Type
National
Awarded By
Genetics Society of America
Date
January 01, 2013

Fellows. American Academy of Arts and Sciences.

Type
National
Awarded By
American Academy of Arts and Sciences
Date
January 01, 2005

Members/ Foreign Associates. National Academy of Science.

Type
National
Awarded By
National Academy of Science
Date
January 01, 1999

Publications:

Global analysis of genomic instability caused by DNA replication stress in Saccharomyces cerevisiae.

DNA replication stress (DRS)-induced genomic instability is an important factor driving cancer development. To understand the mechanisms of DRS-associated genomic instability, we measured the rates of genomic alterations throughout the genome in a yeast strain with lowered expression of the replicative DNA polymerase δ. By a genetic test, we showed that most recombinogenic DNA lesions were introduced during S or G2 phase, presumably as a consequence of broken replication forks. We observed a high rate of chromosome loss, likely reflecting a reduced capacity of the low-polymerase strains to repair double-stranded DNA breaks (DSBs). We also observed a high frequency of deletion events within tandemly repeated genes such as the ribosomal RNA genes. By whole-genome sequencing, we found that low levels of DNA polymerase δ elevated mutation rates, both single-base mutations and small insertions/deletions. Finally, we showed that cells with low levels of DNA polymerase δ tended to accumulate small promoter mutations that increased the expression of this polymerase. These deletions conferred a selective growth advantage to cells, demonstrating that DRS can be one factor driving phenotypic evolution.

Authors
Zheng, D-Q; Zhang, K; Wu, X-C; Mieczkowski, PA; Petes, TD
MLA Citation
Zheng, D-Q, Zhang, K, Wu, X-C, Mieczkowski, PA, and Petes, TD. "Global analysis of genomic instability caused by DNA replication stress in Saccharomyces cerevisiae." Proceedings of the National Academy of Sciences of the United States of America 113.50 (December 2016): E8114-E8121.
PMID
27911848
Source
epmc
Published In
Proceedings of the National Academy of Sciences of USA
Volume
113
Issue
50
Publish Date
2016
Start Page
E8114
End Page
E8121

High-Resolution Mapping of Homologous Recombination Events in rad3 Hyper-Recombination Mutants in Yeast.

The Saccharomyces cerevisae RAD3 gene is the homolog of human XPD, an essential gene encoding a DNA helicase of the TFIIH complex involved in both nucleotide excision repair (NER) and transcription. Some mutant alleles of RAD3 (rad3-101 and rad3-102) have partial defects in DNA repair and a strong hyper-recombination (hyper-Rec) phenotype. Previous studies showed that the hyper-Rec phenotype associated with rad3-101 and rad3-102 can be explained as a consequence of persistent single-stranded DNA gaps that are converted to recombinogenic double-strand breaks (DSBs) by replication. The systems previously used to characterize the hyper-Rec phenotype of rad3 strains do not detect the reciprocal products of mitotic recombination. We have further characterized these events using a system in which the reciprocal products of mitotic recombination are recovered. Both rad3-101 and rad3-102 elevate the frequency of reciprocal crossovers about 100-fold. Mapping of these events shows that three-quarters of these crossovers reflect DSBs formed at the same positions in both sister chromatids (double sister-chromatid breaks, DSCBs). The remainder reflects DSBs formed in single chromatids (single chromatid breaks, SCBs). The ratio of DSCBs to SCBs is similar to that observed for spontaneous recombination events in wild-type cells. We mapped 216 unselected genomic alterations throughout the genome including crossovers, gene conversions, deletions, and duplications. We found a significant association between the location of these recombination events and regions with elevated gamma-H2AX. In addition, there was a hotspot for deletions and duplications at the IMA2 and HXT11 genes near the left end of chromosome XV. A comparison of these data with our previous analysis of spontaneous mitotic recombination events suggests that a sub-set of spontaneous events in wild-type cells may be initiated by incomplete NER reactions, and that DSCBs, which cannot be repaired by sister-chromatid recombination, are a major source of mitotic recombination between homologous chromosomes.

Authors
Andersen, SL; Zhang, A; Dominska, M; Moriel-Carretero, M; Herrera-Moyano, E; Aguilera, A; Petes, TD
MLA Citation
Andersen, SL, Zhang, A, Dominska, M, Moriel-Carretero, M, Herrera-Moyano, E, Aguilera, A, and Petes, TD. "High-Resolution Mapping of Homologous Recombination Events in rad3 Hyper-Recombination Mutants in Yeast." PLoS genetics 12.3 (March 11, 2016): e1005938-.
PMID
26968037
Source
epmc
Published In
PLoS genetics
Volume
12
Issue
3
Publish Date
2016
Start Page
e1005938
DOI
10.1371/journal.pgen.1005938

Elevated Genome-Wide Instability in Yeast Mutants Lacking RNase H Activity.

Two types of RNA:DNA associations can lead to genome instability: the formation of R-loops during transcription and the incorporation of ribonucleotide monophosphates (rNMPs) into DNA during replication. Both ribonuclease (RNase) H1 and RNase H2 degrade the RNA component of R-loops, whereas only RNase H2 can remove one or a few rNMPs from DNA. We performed high-resolution mapping of mitotic recombination events throughout the yeast genome in diploid strains of Saccharomyces cerevisiae lacking RNase H1 (rnh1Δ), RNase H2 (rnh201Δ), or both RNase H1 and RNase H2 (rnh1Δ rnh201Δ). We found little effect on recombination in the rnh1Δ strain, but elevated recombination in both the rnh201Δ and the double-mutant strains; levels of recombination in the double mutant were ∼50% higher than in the rnh201 single-mutant strain. An rnh201Δ mutant that additionally contained a mutation that reduces rNMP incorporation by DNA polymerase ε (pol2-M644L) had a level of instability similar to that observed in the presence of wild-type Pol ε. This result suggests that the elevated recombination observed in the absence of only RNase H2 is primarily a consequence of R-loops rather than misincorporated rNMPs.

Authors
O'Connell, K; Jinks-Robertson, S; Petes, TD
MLA Citation
O'Connell, K, Jinks-Robertson, S, and Petes, TD. "Elevated Genome-Wide Instability in Yeast Mutants Lacking RNase H Activity." Genetics 201.3 (November 2015): 963-975.
PMID
26400613
Source
epmc
Published In
Genetics
Volume
201
Issue
3
Publish Date
2015
Start Page
963
End Page
975
DOI
10.1534/genetics.115.182725

Mre11-Sae2 and RPA Collaborate to Prevent Palindromic Gene Amplification.

Foldback priming at DNA double-stranded breaks is one mechanism proposed to initiate palindromic gene amplification, a common feature of cancer cells. Here, we show that small (5-9 bp) inverted repeats drive the formation of large palindromic duplications, the major class of chromosomal rearrangements recovered from yeast cells lacking Sae2 or the Mre11 nuclease. RPA dysfunction increased the frequency of palindromic duplications in Sae2 or Mre11 nuclease-deficient cells by ∼ 1,000-fold, consistent with intra-strand annealing to create a hairpin-capped chromosome that is subsequently replicated to form a dicentric isochromosome. The palindromic duplications were frequently associated with duplication of a second chromosome region bounded by a repeated sequence and a telomere, suggesting the dicentric chromosome breaks and repairs by recombination between dispersed repeats to acquire a telomere. We propose secondary structures within single-stranded DNA are potent instigators of genome instability, and RPA and Mre11-Sae2 play important roles in preventing their formation and propagation, respectively.

Authors
Deng, SK; Yin, Y; Petes, TD; Symington, LS
MLA Citation
Deng, SK, Yin, Y, Petes, TD, and Symington, LS. "Mre11-Sae2 and RPA Collaborate to Prevent Palindromic Gene Amplification." Molecular cell 60.3 (November 2015): 500-508.
PMID
26545079
Source
epmc
Published In
Molecular Cell
Volume
60
Issue
3
Publish Date
2015
Start Page
500
End Page
508
DOI
10.1016/j.molcel.2015.09.027

The Transient Inactivation of the Master Cell Cycle Phosphatase Cdc14 Causes Genomic Instability in Diploid Cells of Saccharomyces cerevisiae.

Genomic instability is a common feature found in cancer cells . Accordingly, many tumor suppressor genes identified in familiar cancer syndromes are involved in the maintenance of the stability of the genome during every cell division and are commonly referred to as caretakers. Inactivating mutations and epigenetic silencing of caretakers are thought to be the most important mechanisms that explain cancer-related genome instability. However, little is known of whether transient inactivation of caretaker proteins could trigger genome instability and, if so, what types of instability would occur. In this work, we show that a brief and reversible inactivation, during just one cell cycle, of the key phosphatase Cdc14 in the model organism Saccharomyces cerevisiae is enough to result in diploid cells with multiple gross chromosomal rearrangements and changes in ploidy. Interestingly, we observed that such transient loss yields a characteristic fingerprint whereby trisomies are often found in small-sized chromosomes, and gross chromosome rearrangements, often associated with concomitant loss of heterozygosity, are detected mainly on the ribosomal DNA-bearing chromosome XII. Taking into account the key role of Cdc14 in preventing anaphase bridges, resetting replication origins, and controlling spindle dynamics in a well-defined window within anaphase, we speculate that the transient loss of Cdc14 activity causes cells to go through a single mitotic catastrophe with irreversible consequences for the genome stability of the progeny.

Authors
Quevedo, O; Ramos-Pérez, C; Petes, TD; Machín, F
MLA Citation
Quevedo, O, Ramos-Pérez, C, Petes, TD, and Machín, F. "The Transient Inactivation of the Master Cell Cycle Phosphatase Cdc14 Causes Genomic Instability in Diploid Cells of Saccharomyces cerevisiae." Genetics 200.3 (July 2015): 755-769.
PMID
25971663
Source
epmc
Published In
Genetics
Volume
200
Issue
3
Publish Date
2015
Start Page
755
End Page
769
DOI
10.1534/genetics.115.177626

Genome-destabilizing effects associated with top1 loss or accumulation of top1 cleavage complexes in yeast.

Topoisomerase 1 (Top1), a Type IB topoisomerase, functions to relieve transcription- and replication-associated torsional stress in DNA. We investigated the effects of Top1 on genome stability in Saccharomyces cerevisiae using two different assays. First, a sectoring assay that detects loss of heterozygosity (LOH) on a specific chromosome was used to measure reciprocal crossover (RCO) rates. Features of individual RCO events were then molecularly characterized using chromosome-specific microarrays. In the second assay, cells were sub-cultured for 250 generations and LOH was examined genome-wide using microarrays. Though loss of Top1 did not destabilize single-copy genomic regions, RCO events were more complex than in a wild-type strain. In contrast to the stability of single-copy regions, sub-culturing experiments revealed that top1 mutants had greatly elevated levels of instability within the tandemly-repeated ribosomal RNA genes (in agreement with previous results). An intermediate in the enzymatic reaction catalyzed by Top1 is the covalent attachment of Top1 to the cleaved DNA. The resulting Top1 cleavage complex (Top1cc) is usually transient but can be stabilized by the drug camptothecin (CPT) or by the top1-T722A allele. We found that increased levels of the Top1cc resulted in a five- to ten-fold increase in RCOs and greatly increased instability within the rDNA and CUP1 tandem arrays. A detailed analysis of the events in strains with elevated levels of Top1cc suggests that recombinogenic DNA lesions are introduced during or after DNA synthesis. These results have important implications for understanding the effects of CPT as a chemotherapeutic agent.

Authors
Andersen, SL; Sloan, RS; Petes, TD; Jinks-Robertson, S
MLA Citation
Andersen, SL, Sloan, RS, Petes, TD, and Jinks-Robertson, S. "Genome-destabilizing effects associated with top1 loss or accumulation of top1 cleavage complexes in yeast." PLoS genetics 11.4 (April 2015): e1005098-.
PMID
25830313
Source
epmc
Published In
PLoS genetics
Volume
11
Issue
4
Publish Date
2015
Start Page
e1005098
DOI
10.1371/journal.pgen.1005098

Recombination between homologous chromosomes induced by unrepaired UV-generated DNA damage requires Mus81p and is suppressed by Mms2p.

DNA lesions caused by UV radiation are highly recombinogenic. In wild-type cells, the recombinogenic effect of UV partially reflects the processing of UV-induced pyrimidine dimers into DNA gaps or breaks by the enzymes of the nucleotide excision repair (NER) pathway. In this study, we show that unprocessed pyrimidine dimers also potently induce recombination between homologs. In NER-deficient rad14 diploid strains, we demonstrate that unexcised pyrimidine dimers stimulate crossovers, noncrossovers, and break-induced replication events. The same dose of UV is about six-fold more recombinogenic in a repair-deficient strain than in a repair-proficient strain. We also examined the roles of several genes involved in the processing of UV-induced damage in NER-deficient cells. We found that the resolvase Mus81p is required for most of the UV-induced inter-homolog recombination events. This requirement likely reflects the Mus81p-associated cleavage of dimer-blocked replication forks. The error-free post-replication repair pathway mediated by Mms2p suppresses dimer-induced recombination between homologs, possibly by channeling replication-blocking lesions into recombination between sister chromatids.

Authors
Yin, Y; Petes, TD
MLA Citation
Yin, Y, and Petes, TD. "Recombination between homologous chromosomes induced by unrepaired UV-generated DNA damage requires Mus81p and is suppressed by Mms2p." PLoS genetics 11.3 (March 4, 2015): e1005026-.
PMID
25738287
Source
epmc
Published In
PLoS genetics
Volume
11
Issue
3
Publish Date
2015
Start Page
e1005026
DOI
10.1371/journal.pgen.1005026

Chromosome rearrangements via template switching between diverged repeated sequences.

Recent high-resolution genome analyses of cancer and other diseases have revealed the occurrence of microhomology-mediated chromosome rearrangements and copy number changes. Although some of these rearrangements appear to involve nonhomologous end-joining, many must have involved mechanisms requiring new DNA synthesis. Models such as microhomology-mediated break-induced replication (MM-BIR) have been invoked to explain these rearrangements. We examined BIR and template switching between highly diverged sequences in Saccharomyces cerevisiae, induced during repair of a site-specific double-strand break (DSB). Our data show that such template switches are robust mechanisms that give rise to complex rearrangements. Template switches between highly divergent sequences appear to be mechanistically distinct from the initial strand invasions that establish BIR. In particular, such jumps are less constrained by sequence divergence and exhibit a different pattern of microhomology junctions. BIR traversing repeated DNA sequences frequently results in complex translocations analogous to those seen in mammalian cells. These results suggest that template switching among repeated genes is a potent driver of genome instability and evolution.

Authors
Anand, RP; Tsaponina, O; Greenwell, PW; Lee, C-S; Du, W; Petes, TD; Haber, JE
MLA Citation
Anand, RP, Tsaponina, O, Greenwell, PW, Lee, C-S, Du, W, Petes, TD, and Haber, JE. "Chromosome rearrangements via template switching between diverged repeated sequences." Genes & development 28.21 (November 2014): 2394-2406.
PMID
25367035
Source
epmc
Published In
Genes & development
Volume
28
Issue
21
Publish Date
2014
Start Page
2394
End Page
2406
DOI
10.1101/gad.250258.114

Structures of naturally evolved CUP1 tandem arrays in yeast indicate that these arrays are generated by unequal nonhomologous recombination.

An important issue in genome evolution is the mechanism by which tandem duplications are generated from single-copy genes. In the yeast Saccharomyces cerevisiae, most strains contain tandemly duplicated copies of CUP1, a gene that encodes a copper-binding metallothionein. By screening 101 natural isolates of S. cerevisiae, we identified five different types of CUP1-containing repeats, as well as strains that only had one copy of CUP1. A comparison of the DNA sequences of these strains indicates that the CUP1 tandem arrays were generated by unequal nonhomologous recombination events from strains that had one CUP1 gene.

Authors
Zhao, Y; Strope, PK; Kozmin, SG; McCusker, JH; Dietrich, FS; Kokoska, RJ; Petes, TD
MLA Citation
Zhao, Y, Strope, PK, Kozmin, SG, McCusker, JH, Dietrich, FS, Kokoska, RJ, and Petes, TD. "Structures of naturally evolved CUP1 tandem arrays in yeast indicate that these arrays are generated by unequal nonhomologous recombination." G3 (Bethesda, Md.) 4.11 (September 17, 2014): 2259-2269.
PMID
25236733
Source
epmc
Published In
G3 (Bethesda, Md.)
Volume
4
Issue
11
Publish Date
2014
Start Page
2259
End Page
2269
DOI
10.1534/g3.114.012922

High-resolution mapping of two types of spontaneous mitotic gene conversion events in Saccharomyces cerevisiae.

Gene conversions and crossovers are related products of the repair of double-stranded DNA breaks by homologous recombination. Most previous studies of mitotic gene conversion events have been restricted to measuring conversion tracts that are <5 kb. Using a genetic assay in which the lengths of very long gene conversion tracts can be measured, we detected two types of conversions: those with a median size of ∼6 kb and those with a median size of >50 kb. The unusually long tracts are initiated at a naturally occurring recombination hotspot formed by two inverted Ty elements. We suggest that these long gene conversion events may be generated by a mechanism (break-induced replication or repair of a double-stranded DNA gap) different from the short conversion tracts that likely reflect heteroduplex formation followed by DNA mismatch repair. Both the short and long mitotic conversion tracts are considerably longer than those observed in meiosis. Since mitotic crossovers in a diploid can result in a heterozygous recessive deleterious mutation becoming homozygous, it has been suggested that the repair of DNA breaks by mitotic recombination involves gene conversion events that are unassociated with crossing over. In contrast to this prediction, we found that ∼40% of the conversion tracts are associated with crossovers. Spontaneous mitotic crossover events in yeast are frequent enough to be an important factor in genome evolution.

Authors
Yim, E; O'Connell, KE; St Charles, J; Petes, TD
MLA Citation
Yim, E, O'Connell, KE, St Charles, J, and Petes, TD. "High-resolution mapping of two types of spontaneous mitotic gene conversion events in Saccharomyces cerevisiae." Genetics 198.1 (September 2014): 181-192.
PMID
24990991
Source
epmc
Published In
Genetics
Volume
198
Issue
1
Publish Date
2014
Start Page
181
End Page
192
DOI
10.1534/genetics.114.167395

The role of Exo1p exonuclease in DNA end resection to generate gene conversion tracts in Saccharomyces cerevisiae.

The yeast Exo1p nuclease functions in multiple cellular roles: resection of DNA ends generated during recombination, telomere stability, DNA mismatch repair, and expansion of gaps formed during the repair of UV-induced DNA damage. In this study, we performed high-resolution mapping of spontaneous and UV-induced recombination events between homologs in exo1 strains, comparing the results with spontaneous and UV-induced recombination events in wild-type strains. One important comparison was the lengths of gene conversion tracts. Gene conversion events are usually interpreted as reflecting heteroduplex formation between interacting DNA molecules, followed by repair of mismatches within the heteroduplex. In most models of recombination, the length of the gene conversion tract is a function of the length of single-stranded DNA generated by end resection. Since the Exo1p has an important role in end resection, a reduction in the lengths of gene conversion tracts in exo1 strains was expected. In accordance with this expectation, gene conversion tract lengths associated with spontaneous crossovers in exo1 strains were reduced about twofold relative to wild type. For UV-induced events, conversion tract lengths associated with crossovers were also shorter for the exo1 strain than for the wild-type strain (3.2 and 7.6 kb, respectively). Unexpectedly, however, the lengths of conversion tracts that were unassociated with crossovers were longer in the exo1 strain than in the wild-type strain (6.2 and 4.8 kb, respectively). Alternative models of recombination in which the lengths of conversion tracts are determined by break-induced replication or oversynthesis during strand invasion are proposed to account for these observations.

Authors
Yin, Y; Petes, TD
MLA Citation
Yin, Y, and Petes, TD. "The role of Exo1p exonuclease in DNA end resection to generate gene conversion tracts in Saccharomyces cerevisiae." Genetics 197.4 (August 2014): 1097-1109.
PMID
24835424
Source
epmc
Published In
Genetics
Volume
197
Issue
4
Publish Date
2014
Start Page
1097
End Page
1109
DOI
10.1534/genetics.114.164517

Genome-wide high-resolution mapping of chromosome fragile sites in Saccharomyces cerevisiae.

In mammalian cells, perturbations in DNA replication result in chromosome breaks in regions termed "fragile sites." Using DNA microarrays, we mapped recombination events and chromosome rearrangements induced by reduced levels of the replicative DNA polymerase-α in the yeast Saccharomyces cerevisiae. We found that the recombination events were nonrandomly associated with a number of structural/sequence motifs that correlate with paused DNA replication forks, including replication-termination sites (TER sites) and binding sites for the helicase Rrm3p. The pattern of gene-conversion events associated with cross-overs suggests that most of the DNA lesions that initiate recombination between homologs are double-stranded DNA breaks induced during S or G2 of the cell cycle, in contrast to spontaneous recombination events that are initiated by double-stranded DNA breaks formed prior to replication. Low levels of DNA polymerase-α also induced very high rates of aneuploidy, as well as chromosome deletions and duplications. Most of the deletions and duplications had Ty retrotransposons at their breakpoints.

Authors
Song, W; Dominska, M; Greenwell, PW; Petes, TD
MLA Citation
Song, W, Dominska, M, Greenwell, PW, and Petes, TD. "Genome-wide high-resolution mapping of chromosome fragile sites in Saccharomyces cerevisiae." Proceedings of the National Academy of Sciences of the United States of America 111.21 (May 5, 2014): E2210-E2218.
PMID
24799712
Source
epmc
Published In
Proceedings of the National Academy of Sciences of USA
Volume
111
Issue
21
Publish Date
2014
Start Page
E2210
End Page
E2218
DOI
10.1073/pnas.1406847111

Genome rearrangements caused by interstitial telomeric sequences in yeast.

Interstitial telomeric sequences (ITSs) are present in many eukaryotic genomes and are linked to genome instabilities and disease in humans. The mechanisms responsible for ITS-mediated genome instability are not understood in molecular detail. Here, we use a model Saccharomyces cerevisiae system to characterize genome instability mediated by yeast telomeric (Ytel) repeats embedded within an intron of a reporter gene inside a yeast chromosome. We observed a very high rate of small insertions and deletions within the repeats. We also found frequent gross chromosome rearrangements, including deletions, duplications, inversions, translocations, and formation of acentric minichromosomes. The inversions are a unique class of chromosome rearrangement involving an interaction between the ITS and the true telomere of the chromosome. Because we previously found that Ytel repeats cause strong replication fork stalling, we suggest that formation of double-stranded DNA breaks within the Ytel sequences might be responsible for these gross chromosome rearrangements.

Authors
Aksenova, AY; Greenwell, PW; Dominska, M; Shishkin, AA; Kim, JC; Petes, TD; Mirkin, SM
MLA Citation
Aksenova, AY, Greenwell, PW, Dominska, M, Shishkin, AA, Kim, JC, Petes, TD, and Mirkin, SM. "Genome rearrangements caused by interstitial telomeric sequences in yeast." Proc Natl Acad Sci U S A 110.49 (December 3, 2013): 19866-19871.
PMID
24191060
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
110
Issue
49
Publish Date
2013
Start Page
19866
End Page
19871
DOI
10.1073/pnas.1319313110

Genome-wide high-resolution mapping of UV-induced mitotic recombination events in Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae and most other eukaryotes, mitotic recombination is important for the repair of double-stranded DNA breaks (DSBs). Mitotic recombination between homologous chromosomes can result in loss of heterozygosity (LOH). In this study, LOH events induced by ultraviolet (UV) light are mapped throughout the genome to a resolution of about 1 kb using single-nucleotide polymorphism (SNP) microarrays. UV doses that have little effect on the viability of diploid cells stimulate crossovers more than 1000-fold in wild-type cells. In addition, UV stimulates recombination in G1-synchronized cells about 10-fold more efficiently than in G2-synchronized cells. Importantly, at high doses of UV, most conversion events reflect the repair of two sister chromatids that are broken at approximately the same position whereas at low doses, most conversion events reflect the repair of a single broken chromatid. Genome-wide mapping of about 380 unselected crossovers, break-induced replication (BIR) events, and gene conversions shows that UV-induced recombination events occur throughout the genome without pronounced hotspots, although the ribosomal RNA gene cluster has a significantly lower frequency of crossovers.

Authors
Yin, Y; Petes, TD
MLA Citation
Yin, Y, and Petes, TD. "Genome-wide high-resolution mapping of UV-induced mitotic recombination events in Saccharomyces cerevisiae." PLoS Genet 9.10 (October 2013): e1003894-.
PMID
24204306
Source
pubmed
Published In
PLoS genetics
Volume
9
Issue
10
Publish Date
2013
Start Page
e1003894
DOI
10.1371/journal.pgen.1003894

Nonrandom distribution of interhomolog recombination events induced by breakage of a dicentric chromosome in Saccharomyces cerevisiae.

Dicentric chromosomes undergo breakage in mitosis, resulting in chromosome deletions, duplications, and translocations. In this study, we map chromosome break sites of dicentrics in Saccharomyces cerevisiae by a mitotic recombination assay. The assay uses a diploid strain in which one homolog has a conditional centromere in addition to a wild-type centromere, and the other homolog has only the wild-type centromere; the conditional centromere is inactive when cells are grown in galactose and is activated when the cells are switched to glucose. In addition, the two homologs are distinguishable by multiple single-nucleotide polymorphisms (SNPs). Under conditions in which the conditional centromere is activated, the functionally dicentric chromosome undergoes double-stranded DNA breaks (DSBs) that can be repaired by mitotic recombination with the homolog. Such recombination events often lead to loss of heterozygosity (LOH) of SNPs that are centromere distal to the crossover. Using a PCR-based assay, we determined the position of LOH in multiple independent recombination events to a resolution of ∼4 kb. This analysis shows that dicentric chromosomes have recombination breakpoints that are broadly distributed between the two centromeres, although there is a clustering of breakpoints within 10 kb of the conditional centromere.

Authors
Song, W; Gawel, M; Dominska, M; Greenwell, PW; Hazkani-Covo, E; Bloom, K; Petes, TD
MLA Citation
Song, W, Gawel, M, Dominska, M, Greenwell, PW, Hazkani-Covo, E, Bloom, K, and Petes, TD. "Nonrandom distribution of interhomolog recombination events induced by breakage of a dicentric chromosome in Saccharomyces cerevisiae." Genetics 194.1 (May 2013): 69-80.
PMID
23410835
Source
pubmed
Published In
Genetics
Volume
194
Issue
1
Publish Date
2013
Start Page
69
End Page
80
DOI
10.1534/genetics.113.150144

High-resolution mapping of spontaneous mitotic recombination hotspots on the 1.1 Mb arm of yeast chromosome IV.

Although homologous recombination is an important pathway for the repair of double-stranded DNA breaks in mitotically dividing eukaryotic cells, these events can also have negative consequences, such as loss of heterozygosity (LOH) of deleterious mutations. We mapped about 140 spontaneous reciprocal crossovers on the right arm of the yeast chromosome IV using single-nucleotide-polymorphism (SNP) microarrays. Our mapping and subsequent experiments demonstrate that inverted repeats of Ty retrotransposable elements are mitotic recombination hotspots. We found that the mitotic recombination maps on the two homologs were substantially different and were unrelated to meiotic recombination maps. Additionally, about 70% of the DNA lesions that result in LOH are likely generated during G1 of the cell cycle and repaired during S or G2. We also show that different genetic elements are associated with reciprocal crossover conversion tracts depending on the cell cycle timing of the initiating DSB.

Authors
St Charles, J; Petes, TD
MLA Citation
St Charles, J, and Petes, TD. "High-resolution mapping of spontaneous mitotic recombination hotspots on the 1.1 Mb arm of yeast chromosome IV." PLoS Genet 9.4 (April 2013): e1003434-.
PMID
23593029
Source
pubmed
Published In
PLoS genetics
Volume
9
Issue
4
Publish Date
2013
Start Page
e1003434
DOI
10.1371/journal.pgen.1003434

Gene copy-number variation in haploid and diploid strains of the yeast Saccharomyces cerevisiae.

The increasing ability to sequence and compare multiple individual genomes within a species has highlighted the fact that copy-number variation (CNV) is a substantial and underappreciated source of genetic diversity. Chromosome-scale mutations occur at rates orders of magnitude higher than base substitutions, yet our understanding of the mechanisms leading to CNVs has been lagging. We examined CNV in a region of chromosome 5 (chr5) in haploid and diploid strains of Saccharomyces cerevisiae. We optimized a CNV detection assay based on a reporter cassette containing the SFA1 and CUP1 genes that confer gene dosage-dependent tolerance to formaldehyde and copper, respectively. This optimized reporter allowed the selection of low-order gene amplification events, going from one copy to two copies in haploids and from two to three copies in diploids. In haploid strains, most events involved tandem segmental duplications mediated by nonallelic homologous recombination between flanking direct repeats, primarily Ty1 elements. In diploids, most events involved the formation of a recurrent nonreciprocal translocation between a chr5 Ty1 element and another Ty1 repeat on chr13. In addition to amplification events, a subset of clones displaying elevated resistance to formaldehyde had point mutations within the SFA1 coding sequence. These mutations were all dominant and are proposed to result in hyperactive forms of the formaldehyde dehydrogenase enzyme.

Authors
Zhang, H; Zeidler, AFB; Song, W; Puccia, CM; Malc, E; Greenwell, PW; Mieczkowski, PA; Petes, TD; Argueso, JL
MLA Citation
Zhang, H, Zeidler, AFB, Song, W, Puccia, CM, Malc, E, Greenwell, PW, Mieczkowski, PA, Petes, TD, and Argueso, JL. "Gene copy-number variation in haploid and diploid strains of the yeast Saccharomyces cerevisiae." Genetics 193.3 (March 2013): 785-801.
PMID
23307895
Source
pubmed
Published In
Genetics
Volume
193
Issue
3
Publish Date
2013
Start Page
785
End Page
801
DOI
10.1534/genetics.112.146522

Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA·TTC) associated with Friedreich's ataxia.

Expansion of certain trinucleotide repeats causes several types of human diseases, and such tracts are associated with the formation of deletions and other types of genetic rearrangements in Escherichia coli, yeast, and mammalian cells. Below, we show that long (230 repeats) tracts of the trinucleotide associated with Friedreich's ataxia (GAA·TTC) stimulate both large (>50 bp) deletions and point mutations in a reporter gene located more than 1 kb from the repetitive tract. Sequence analysis of deletion breakpoints indicates that the deletions reflect non-homologous end joining of double-stranded DNA breaks (DSBs) initiated in the tract. The tract-induced point mutations appear to reflect a different mechanism involving single-strand annealing of DNA molecules generated by DSBs within the tract, followed by filling-in of single-stranded gaps by the error-prone DNA polymerase zeta.

Authors
Tang, W; Dominska, M; Gawel, M; Greenwell, PW; Petes, TD
MLA Citation
Tang, W, Dominska, M, Gawel, M, Greenwell, PW, and Petes, TD. "Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA·TTC) associated with Friedreich's ataxia." DNA Repair (Amst) 12.1 (January 1, 2013): 10-17.
PMID
23182423
Source
pubmed
Published In
DNA Repair
Volume
12
Issue
1
Publish Date
2013
Start Page
10
End Page
17
DOI
10.1016/j.dnarep.2012.10.001

Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA·TTC) associated with Friedreich's ataxia

Expansion of certain trinucleotide repeats causes several types of human diseases, and such tracts are associated with the formation of deletions and other types of genetic rearrangements in Escherichia coli, yeast, and mammalian cells. Below, we show that long (230 repeats) tracts of the trinucleotide associated with Friedreich's ataxia (GAA·TTC) stimulate both large (>50. bp) deletions and point mutations in a reporter gene located more than 1. kb from the repetitive tract. Sequence analysis of deletion breakpoints indicates that the deletions reflect non-homologous end joining of double-stranded DNA breaks (DSBs) initiated in the tract. The tract-induced point mutations appear to reflect a different mechanism involving single-strand annealing of DNA molecules generated by DSBs within the tract, followed by filling-in of single-stranded gaps by the error-prone DNA polymerase zeta. © 2012 Elsevier B.V.

Authors
Tang, W; Dominska, M; Gawel, M; Greenwell, PW; Petes, TD
MLA Citation
Tang, W, Dominska, M, Gawel, M, Greenwell, PW, and Petes, TD. "Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA·TTC) associated with Friedreich's ataxia." DNA Repair 12.1 (2013): 10-17.
Source
scival
Published In
DNA Repair
Volume
12
Issue
1
Publish Date
2013
Start Page
10
End Page
17
DOI
10.1016/j.dnarep.2012.10.001

The 2013 Thomas Hunt Morgan Medal

The Genetics Society of America annually honors members who have made outstanding contributions to genetics. The Thomas Hunt Morgan Medal recognizes a lifetime contribution to the science of genetics. The Genetics Society of America Medal recognizes particularly outstanding contributions to the science of genetics over the past 32 years. The George W. Beadle Award recognizes distinguished service to the field of genetics and the community of geneticists. The Elizabeth W. Jones Award for Excellence in Education recognizes individuals or groups who have had a significant, sustained impact on genetics education at any level, from kindergarten through graduate school and beyond. The Novitski Prize recognizes an extraordinary level of creativity and intellectual ingenuity in solving significant problems in biological research through the application of genetic methods. We are pleased to announce the 2013 awards. © 2013 by the Genetics Society of America.

Authors
Petes, TD; Jinks-Robertson, S; Hieter, P
MLA Citation
Petes, TD, Jinks-Robertson, S, and Hieter, P. "The 2013 Thomas Hunt Morgan Medal." Genetics 194.1 (2013): 1-4.
PMID
23633133
Source
scival
Published In
Genetics
Volume
194
Issue
1
Publish Date
2013
Start Page
1
End Page
4
DOI
10.1534/genetics.113.150664

Reciprocal uniparental disomy in yeast.

In the diploid cells of most organisms, including humans, each chromosome is usually distinguishable from its partner homolog by multiple single-nucleotide polymorphisms. One common type of genetic alteration observed in tumor cells is uniparental disomy (UPD), in which a pair of homologous chromosomes are derived from a single parent, resulting in loss of heterozygosity for all single-nucleotide polymorphisms while maintaining diploidy. Somatic UPD events are usually explained as reflecting two consecutive nondisjunction events. Here we report a previously undescribed mode of chromosome segregation in Saccharomyces cerevisiae in which one cell division produces daughter cells with reciprocal UPD for the same pair of chromosomes without an aneuploid intermediate. One pair of sister chromatids is segregated into one daughter cell and the other pair is segregated into the other daughter cell, mimicking a meiotic chromosome segregation pattern. We term this process "reciprocal uniparental disomy."

Authors
Andersen, SL; Petes, TD
MLA Citation
Andersen, SL, and Petes, TD. "Reciprocal uniparental disomy in yeast." Proc Natl Acad Sci U S A 109.25 (June 19, 2012): 9947-9952.
PMID
22665764
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
109
Issue
25
Publish Date
2012
Start Page
9947
End Page
9952
DOI
10.1073/pnas.1207736109

Haploidization in Saccharomyces cerevisiae induced by a deficiency in homologous recombination.

Diploid Saccharomyes cerevisae strains lacking the RAD52 gene required for homologous recombination have a very high rate of chromosome loss. Two of four isolates subcultured ∼20 times (∼500 cell divisions) became haploid. These strains were capable of mating with wild-type haploids to produce diploid progeny capable of undergoing meiosis to produce four viable spores.

Authors
Song, W; Petes, TD
MLA Citation
Song, W, and Petes, TD. "Haploidization in Saccharomyces cerevisiae induced by a deficiency in homologous recombination." Genetics 191.1 (May 2012): 279-284.
PMID
22367034
Source
pubmed
Published In
Genetics
Volume
191
Issue
1
Publish Date
2012
Start Page
279
End Page
284
DOI
10.1534/genetics.111.138180

High-resolution genome-wide analysis of irradiated (UV and γ-rays) diploid yeast cells reveals a high frequency of genomic loss of heterozygosity (LOH) events.

In diploid eukaryotes, repair of double-stranded DNA breaks by homologous recombination often leads to loss of heterozygosity (LOH). Most previous studies of mitotic recombination in Saccharomyces cerevisiae have focused on a single chromosome or a single region of one chromosome at which LOH events can be selected. In this study, we used two techniques (single-nucleotide polymorphism microarrays and high-throughput DNA sequencing) to examine genome-wide LOH in a diploid yeast strain at a resolution averaging 1 kb. We examined both selected LOH events on chromosome V and unselected events throughout the genome in untreated cells and in cells treated with either γ-radiation or ultraviolet (UV) radiation. Our analysis shows the following: (1) spontaneous and damage-induced mitotic gene conversion tracts are more than three times larger than meiotic conversion tracts, and conversion tracts associated with crossovers are usually longer and more complex than those unassociated with crossovers; (2) most of the crossovers and conversions reflect the repair of two sister chromatids broken at the same position; and (3) both UV and γ-radiation efficiently induce LOH at doses of radiation that cause no significant loss of viability. Using high-throughput DNA sequencing, we also detected new mutations induced by γ-rays and UV. To our knowledge, our study represents the first high-resolution genome-wide analysis of DNA damage-induced LOH events performed in any eukaryote.

Authors
St Charles, J; Hazkani-Covo, E; Yin, Y; Andersen, SL; Dietrich, FS; Greenwell, PW; Malc, E; Mieczkowski, P; Petes, TD
MLA Citation
St Charles, J, Hazkani-Covo, E, Yin, Y, Andersen, SL, Dietrich, FS, Greenwell, PW, Malc, E, Mieczkowski, P, and Petes, TD. "High-resolution genome-wide analysis of irradiated (UV and γ-rays) diploid yeast cells reveals a high frequency of genomic loss of heterozygosity (LOH) events." Genetics 190.4 (April 2012): 1267-1284.
PMID
22267500
Source
pubmed
Published In
Genetics
Volume
190
Issue
4
Publish Date
2012
Start Page
1267
End Page
1284
DOI
10.1534/genetics.111.137927

Friedreich's ataxia (GAA)n•(TTC)n repeats strongly stimulate mitotic crossovers in Saccharomyces cerevisae.

Expansions of trinucleotide GAA•TTC tracts are associated with the human disease Friedreich's ataxia, and long GAA•TTC tracts elevate genome instability in yeast. We show that tracts of (GAA)(230)•(TTC)(230) stimulate mitotic crossovers in yeast about 10,000-fold relative to a "normal" DNA sequence; (GAA)(n)•(TTC)(n) tracts, however, do not significantly elevate meiotic recombination. Most of the mitotic crossovers are associated with a region of non-reciprocal transfer of information (gene conversion). The major class of recombination events stimulated by (GAA)(n)•(TTC)(n) tracts is a tract-associated double-strand break (DSB) that occurs in unreplicated chromosomes, likely in G1 of the cell cycle. These findings indicate that (GAA)(n)•(TTC)(n) tracts can be a potent source of loss of heterozygosity in yeast.

Authors
Tang, W; Dominska, M; Greenwell, PW; Harvanek, Z; Lobachev, KS; Kim, H-M; Narayanan, V; Mirkin, SM; Petes, TD
MLA Citation
Tang, W, Dominska, M, Greenwell, PW, Harvanek, Z, Lobachev, KS, Kim, H-M, Narayanan, V, Mirkin, SM, and Petes, TD. "Friedreich's ataxia (GAA)n•(TTC)n repeats strongly stimulate mitotic crossovers in Saccharomyces cerevisae. (Published online)" PLoS Genet 7.1 (January 13, 2011): e1001270-.
PMID
21249181
Source
pubmed
Published In
PLoS genetics
Volume
7
Issue
1
Publish Date
2011
Start Page
e1001270
DOI
10.1371/journal.pgen.1001270

Meiotic chromosome segregation in triploid strains of Saccharomyces cerevisiae.

Meiosis in triploids results in four highly aneuploid gametes because six copies of each homolog must be segregated into four meiotic products. Using DNA microarrays and other physical approaches, we examined meiotic chromosome segregation in triploid strains of Saccharomyces cerevisiae. In most tetrads with four viable spores, two of the spores had two copies of a given homolog and two spores had only one copy. Chromosomes segregated randomly into viable spores without preferences for generating near haploid or near diploid spores. Using single-nucleotide polymorphisms, we showed that, in most tetrads, all three pairs of homologs recombined. Strains derived from some of the aneuploid spore colonies had very high frequencies of mitotic chromosome loss, resulting in genetically diverse populations of cells.

Authors
St Charles, J; Hamilton, ML; Petes, TD
MLA Citation
St Charles, J, Hamilton, ML, and Petes, TD. "Meiotic chromosome segregation in triploid strains of Saccharomyces cerevisiae." Genetics 186.2 (October 2010): 537-550.
PMID
20697121
Source
pubmed
Published In
Genetics
Volume
186
Issue
2
Publish Date
2010
Start Page
537
End Page
550
DOI
10.1534/genetics.110.121533

Chromosome rearrangements and aneuploidy in yeast strains lacking both Tel1p and Mec1p reflect deficiencies in two different mechanisms.

The human ATM and ATR proteins participate in the DNA damage and DNA replication checkpoint pathways and are critical to maintaining genome stability. The Saccharomyces cerevisiae homologs of ATM and ATR are Tel1p and Mec1p, respectively. Haploid tel1 mec1 strains have very short telomeres and very high rates of chromosomal aberrations. Here, we examine genetic stability in tel1 mec1 diploid cells. In the absence of induced DNA damage, these yeast strains had very high frequencies of aneuploidy (both trisomy and monosomy) in addition to elevated rates of chromosome rearrangements. Although we found the aneuploidy in the tel1 mec1 diploids mimicked that observed in bub1 diploids, the tel1 mec1 diploids had a functional spindle assembly checkpoint. Restoration of wild-type telomere lengths in the tel1 mec1 strain substantially reduced the rate of chromosome rearrangements but had no effect on the frequency of aneuploidy.

Authors
McCulley, JL; Petes, TD
MLA Citation
McCulley, JL, and Petes, TD. "Chromosome rearrangements and aneuploidy in yeast strains lacking both Tel1p and Mec1p reflect deficiencies in two different mechanisms." Proc Natl Acad Sci U S A 107.25 (June 22, 2010): 11465-11470.
PMID
20534547
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
107
Issue
25
Publish Date
2010
Start Page
11465
End Page
11470
DOI
10.1073/pnas.1006281107

From the Cover: mitotic gene conversion events induced in G1-synchronized yeast cells by gamma rays are similar to spontaneous conversion events.

In a previous study, we mapped spontaneous mitotic reciprocal crossovers (RCOs) in a 120-kb interval of chromosome V of Saccharomyces cerevisiae. About three-quarters of the crossovers were associated with gene conversion tracts. About 40% of these conversion tracts had the pattern expected as a consequence of repair of a double-stranded DNA break (DSB) of an unreplicated chromosome. We test this hypothesis by examining the crossovers and gene conversion events induced by gamma irradiation in G1- and G2-arrested diploid yeast cells. The gene conversion patterns of G1-irradiated cells (but not G2-irradiated cells) mimic conversion events associated with spontaneous RCOs, confirming our previous conclusion that many spontaneous crossovers are initiated by a DSB on an unreplicated chromosome.

Authors
Lee, PS; Petes, TD
MLA Citation
Lee, PS, and Petes, TD. "From the Cover: mitotic gene conversion events induced in G1-synchronized yeast cells by gamma rays are similar to spontaneous conversion events." Proc Natl Acad Sci U S A 107.16 (April 20, 2010): 7383-7388.
PMID
20231456
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
107
Issue
16
Publish Date
2010
Start Page
7383
End Page
7388
DOI
10.1073/pnas.1001940107

Genome structure of a Saccharomyces cerevisiae strain widely used in bioethanol production.

Bioethanol is a biofuel produced mainly from the fermentation of carbohydrates derived from agricultural feedstocks by the yeast Saccharomyces cerevisiae. One of the most widely adopted strains is PE-2, a heterothallic diploid naturally adapted to the sugar cane fermentation process used in Brazil. Here we report the molecular genetic analysis of a PE-2 derived diploid (JAY270), and the complete genome sequence of a haploid derivative (JAY291). The JAY270 genome is highly heterozygous (approximately 2 SNPs/kb) and has several structural polymorphisms between homologous chromosomes. These chromosomal rearrangements are confined to the peripheral regions of the chromosomes, with breakpoints within repetitive DNA sequences. Despite its complex karyotype, this diploid, when sporulated, had a high frequency of viable spores. Hybrid diploids formed by outcrossing with the laboratory strain S288c also displayed good spore viability. Thus, the rearrangements that exist near the ends of chromosomes do not impair meiosis, as they do not span regions that contain essential genes. This observation is consistent with a model in which the peripheral regions of chromosomes represent plastic domains of the genome that are free to recombine ectopically and experiment with alternative structures. We also explored features of the JAY270 and JAY291 genomes that help explain their high adaptation to industrial environments, exhibiting desirable phenotypes such as high ethanol and cell mass production and high temperature and oxidative stress tolerance. The genomic manipulation of such strains could enable the creation of a new generation of industrial organisms, ideally suited for use as delivery vehicles for future bioenergy technologies.

Authors
Argueso, JL; Carazzolle, MF; Mieczkowski, PA; Duarte, FM; Netto, OVC; Missawa, SK; Galzerani, F; Costa, GGL; Vidal, RO; Noronha, MF; Dominska, M; Andrietta, MGS; Andrietta, SR; Cunha, AF; Gomes, LH; Tavares, FCA; Alcarde, AR; Dietrich, FS; McCusker, JH; Petes, TD; Pereira, GAG
MLA Citation
Argueso, JL, Carazzolle, MF, Mieczkowski, PA, Duarte, FM, Netto, OVC, Missawa, SK, Galzerani, F, Costa, GGL, Vidal, RO, Noronha, MF, Dominska, M, Andrietta, MGS, Andrietta, SR, Cunha, AF, Gomes, LH, Tavares, FCA, Alcarde, AR, Dietrich, FS, McCusker, JH, Petes, TD, and Pereira, GAG. "Genome structure of a Saccharomyces cerevisiae strain widely used in bioethanol production." Genome Res 19.12 (December 2009): 2258-2270.
PMID
19812109
Source
pubmed
Published In
Genome research
Volume
19
Issue
12
Publish Date
2009
Start Page
2258
End Page
2270
DOI
10.1101/gr.091777.109

Chromosome aberrations resulting from double-strand DNA breaks at a naturally occurring yeast fragile site composed of inverted ty elements are independent of Mre11p and Sae2p.

Genetic instability at palindromes and spaced inverted repeats (IRs) leads to chromosome rearrangements. Perfect palindromes and IRs with short spacers can extrude as cruciforms or fold into hairpins on the lagging strand during replication. Cruciform resolution produces double-strand breaks (DSBs) with hairpin-capped ends, and Mre11p and Sae2p are required to cleave the hairpin tips to facilitate homologous recombination. Fragile site 2 (FS2) is a naturally occurring IR in Saccharomyces cerevisiae composed of a pair of Ty1 elements separated by approximately 280 bp. Our results suggest that FS2 forms a hairpin, rather than a cruciform, during replication in cells with low levels of DNA polymerase. Cleavage of this hairpin results in a recombinogenic DSB. We show that DSB formation at FS2 does not require Mre11p, Sae2p, Rad1p, Slx4p, Pso2p, Exo1p, Mus81p, Yen1p, or Rad27p. Also, repair of DSBs by homologous recombination is efficient in mre11 and sae2 mutants. Homologous recombination is impaired at FS2 in rad52 mutants and most aberrations reflect either joining of two broken chromosomes in a "half crossover" or telomere capping of the break. In support of hairpin formation precipitating DSBs at FS2, two telomere-capped deletions had a breakpoint near the center of the IR. In summary, Mre11p and Sae2p are not required for DSB formation at FS2 or the subsequent repair of these DSBs.

Authors
Casper, AM; Greenwell, PW; Tang, W; Petes, TD
MLA Citation
Casper, AM, Greenwell, PW, Tang, W, and Petes, TD. "Chromosome aberrations resulting from double-strand DNA breaks at a naturally occurring yeast fragile site composed of inverted ty elements are independent of Mre11p and Sae2p." Genetics 183.2 (October 2009): 423-26SI.
PMID
19635935
Source
pubmed
Published In
Genetics
Volume
183
Issue
2
Publish Date
2009
Start Page
423
End Page
26SI
DOI
10.1534/genetics.109.106385

A fine-structure map of spontaneous mitotic crossovers in the yeast Saccharomyces cerevisiae.

Homologous recombination is an important mechanism for the repair of DNA damage in mitotically dividing cells. Mitotic crossovers between homologues with heterozygous alleles can produce two homozygous daughter cells (loss of heterozygosity), whereas crossovers between repeated genes on non-homologous chromosomes can result in translocations. Using a genetic system that allows selection of daughter cells that contain the reciprocal products of mitotic crossing over, we mapped crossovers and gene conversion events at a resolution of about 4 kb in a 120-kb region of chromosome V of Saccharomyces cerevisiae. The gene conversion tracts associated with mitotic crossovers are much longer (averaging about 12 kb) than the conversion tracts associated with meiotic recombination and are non-randomly distributed along the chromosome. In addition, about 40% of the conversion events have patterns of marker segregation that are most simply explained as reflecting the repair of a chromosome that was broken in G1 of the cell cycle.

Authors
Lee, PS; Greenwell, PW; Dominska, M; Gawel, M; Hamilton, M; Petes, TD
MLA Citation
Lee, PS, Greenwell, PW, Dominska, M, Gawel, M, Hamilton, M, and Petes, TD. "A fine-structure map of spontaneous mitotic crossovers in the yeast Saccharomyces cerevisiae." PLoS Genet 5.3 (March 2009): e1000410-.
PMID
19282969
Source
pubmed
Published In
PLoS genetics
Volume
5
Issue
3
Publish Date
2009
Start Page
e1000410
DOI
10.1371/journal.pgen.1000410

Chromosome fragility at GAA tracts in yeast depends on repeat orientation and requires mismatch repair.

Expansion of triplex-forming GAA/TTC repeats in the first intron of FXN gene results in Friedreich's ataxia. Besides FXN, there are a number of other polymorphic GAA/TTC loci in the human genome where the size variations thus far have been considered to be a neutral event. Using yeast as a model system, we demonstrate that expanded GAA/TTC repeats represent a threat to eukaryotic genome integrity by triggering double-strand breaks and gross chromosomal rearrangements. The fragility potential strongly depends on the length of the tracts and orientation of the repeats relative to the replication origin, which correlates with their propensity to adopt triplex structure and to block replication progression. We show that fragility is mediated by mismatch repair machinery and requires the MutSbeta and endonuclease activity of MutLalpha. We suggest that the mechanism of GAA/TTC-induced chromosomal aberrations defined in yeast can also operate in human carriers with expanded tracts.

Authors
Kim, H-M; Narayanan, V; Mieczkowski, PA; Petes, TD; Krasilnikova, MM; Mirkin, SM; Lobachev, KS
MLA Citation
Kim, H-M, Narayanan, V, Mieczkowski, PA, Petes, TD, Krasilnikova, MM, Mirkin, SM, and Lobachev, KS. "Chromosome fragility at GAA tracts in yeast depends on repeat orientation and requires mismatch repair." EMBO J 27.21 (November 5, 2008): 2896-2906.
PMID
18833189
Source
pubmed
Published In
EMBO Journal
Volume
27
Issue
21
Publish Date
2008
Start Page
2896
End Page
2906
DOI
10.1038/emboj.2008.205

Chronic oxidative DNA damage due to DNA repair defects causes chromosomal instability in Saccharomyces cerevisiae.

Oxidative DNA damage is likely to be involved in the etiology of cancer and is thought to accelerate tumorigenesis via increased mutation rates. However, the majority of malignant cells acquire a specific type of genomic instability characterized by large-scale genomic rearrangements, referred to as chromosomal instability (CIN). The molecular mechanisms underlying CIN are not entirely understood. We utilized Saccharomyces cerevisiae as a model system to delineate the relationship between genotoxic stress and CIN. It was found that elevated levels of chronic, unrepaired oxidative DNA damage caused chromosomal aberrations at remarkably high frequencies under both selective and nonselective growth conditions. In this system, exceeding the cellular capacity to appropriately manage oxidative DNA damage resulted in a "gain-of-CIN" phenotype and led to profound karyotypic instability. These results illustrate a novel mechanism for genome destabilization that is likely to be relevant to human carcinogenesis.

Authors
Degtyareva, NP; Chen, L; Mieczkowski, P; Petes, TD; Doetsch, PW
MLA Citation
Degtyareva, NP, Chen, L, Mieczkowski, P, Petes, TD, and Doetsch, PW. "Chronic oxidative DNA damage due to DNA repair defects causes chromosomal instability in Saccharomyces cerevisiae." Mol Cell Biol 28.17 (September 2008): 5432-5445.
PMID
18591251
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
28
Issue
17
Publish Date
2008
Start Page
5432
End Page
5445
DOI
10.1128/MCB.00307-08

Reduced levels of DNA polymerase delta induce chromosome fragile site instability in yeast.

Specific regions of genomes (fragile sites) are hot spots for the chromosome rearrangements that are associated with many types of cancer cells. Understanding the molecular mechanisms regulating the stability of chromosome fragile sites, therefore, has important implications in cancer biology. We previously identified two chromosome fragile sites in Saccharomyces cerevisiae that were induced in response to the reduced expression of Pol1p, the catalytic subunit of DNA polymerase alpha. In the study presented here, we show that reduced levels of Pol3p, the catalytic subunit of DNA polymerase delta, induce instability at these same sites and lead to the generation of a variety of chromosomal aberrations. These findings demonstrate that a change in the stoichiometry of replicative DNA polymerases results in recombinogenic DNA lesions, presumably double-strand DNA breaks.

Authors
Lemoine, FJ; Degtyareva, NP; Kokoska, RJ; Petes, TD
MLA Citation
Lemoine, FJ, Degtyareva, NP, Kokoska, RJ, and Petes, TD. "Reduced levels of DNA polymerase delta induce chromosome fragile site instability in yeast." Mol Cell Biol 28.17 (September 2008): 5359-5368.
PMID
18591249
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
28
Issue
17
Publish Date
2008
Start Page
5359
End Page
5368
DOI
10.1128/MCB.02084-07

Double-strand breaks associated with repetitive DNA can reshape the genome.

Ionizing radiation is an established source of chromosome aberrations (CAs). Although double-strand breaks (DSBs) are implicated in radiation-induced and other CAs, the underlying mechanisms are poorly understood. Here, we show that, although the vast majority of randomly induced DSBs in G(2) diploid yeast cells are repaired efficiently through homologous recombination (HR) between sister chromatids or homologous chromosomes, approximately 2% of all DSBs give rise to CAs. Complete molecular analysis of the genome revealed that nearly all of the CAs resulted from HR between nonallelic repetitive elements, primarily Ty retrotransposons. Nonhomologous end-joining (NHEJ) accounted for few, if any, of the CAs. We conclude that only those DSBs that fall at the 3-5% of the genome composed of repetitive DNA elements are efficient at generating rearrangements with dispersed small repeats across the genome, whereas DSBs in unique sequences are confined to recombinational repair between the large regions of homology contained in sister chromatids or homologous chromosomes. Because repeat-associated DSBs can efficiently lead to CAs and reshape the genome, they could be a rich source of evolutionary change.

Authors
Argueso, JL; Westmoreland, J; Mieczkowski, PA; Gawel, M; Petes, TD; Resnick, MA
MLA Citation
Argueso, JL, Westmoreland, J, Mieczkowski, PA, Gawel, M, Petes, TD, and Resnick, MA. "Double-strand breaks associated with repetitive DNA can reshape the genome." Proc Natl Acad Sci U S A 105.33 (August 19, 2008): 11845-11850.
PMID
18701715
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
105
Issue
33
Publish Date
2008
Start Page
11845
End Page
11850
DOI
10.1073/pnas.0804529105

The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae.

The rate of meiotic recombination in the yeast Saccharomyces cerevisiae varies widely in different regions of the genome with some genes having very high levels of recombination (hotspots). A variety of experiments done in yeast suggest that hotspots are a feature of chromatin structure rather than a feature of primary DNA sequence. We examined the effects of mutating a variety of enzymes that affect chromatin structure on the recombination activity of the well-characterized HIS4 hotspot including the Set2p and Dot1p histone methylases, the Hda1p and Rpd3p histone deacetylases, the Sin4p global transcription regulator, and a deletion of one of the two copies of the genes encoding histone H3-H4. Loss of Set2p or Rpd3p substantially elevated HIS4 hotspot activity, and loss of Hda1p had a smaller stimulatory effect; none of the other alterations had a significant effect. The increase of HIS4 hotspot activity in set2 and rpd3 strains is likely to be related to the recent finding that histone H3 methylation by Set2p directs deacetylation of histones by Rpd3p.

Authors
Merker, JD; Dominska, M; Greenwell, PW; Rinella, E; Bouck, DC; Shibata, Y; Strahl, BD; Mieczkowski, P; Petes, TD
MLA Citation
Merker, JD, Dominska, M, Greenwell, PW, Rinella, E, Bouck, DC, Shibata, Y, Strahl, BD, Mieczkowski, P, and Petes, TD. "The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae." DNA Repair (Amst) 7.8 (August 2, 2008): 1298-1308.
PMID
18515193
Source
pubmed
Published In
DNA Repair
Volume
7
Issue
8
Publish Date
2008
Start Page
1298
End Page
1308
DOI
10.1016/j.dnarep.2008.04.009

Low levels of DNA polymerase alpha induce mitotic and meiotic instability in the ribosomal DNA gene cluster of Saccharomyces cerevisiae.

The ribosomal DNA (rDNA) genes of Saccharomyces cerevisiae are located in a tandem array of about 150 repeats. Using a diploid with markers flanking and within the rDNA array, we showed that low levels of DNA polymerase alpha elevate recombination between both homologues and sister chromatids, about five-fold in mitotic cells and 30-fold in meiotic cells. This stimulation is independent of Fob1p, a protein required for the programmed replication fork block (RFB) in the rDNA. We observed that the fob1 mutation alone significantly increased meiotic, but not mitotic, rDNA recombination, suggesting a meiosis-specific role for this protein. We found that meiotic cells with low polymerase alpha had decreased Sir2p binding and increased Spo11p-catalyzed double-strand DNA breaks in the rDNA. Furthermore, meiotic crossover interference in the rDNA is absent. These results suggest that the hyper-Rec phenotypes resulting from low levels of DNA polymerase alpha in mitosis and meiosis reflect two fundamentally different mechanisms: the increased mitotic recombination is likely due to increased double-strand DNA breaks (DSBs) resulting from Fob1p-independent stalled replication forks, whereas the hyper-Rec meiotic phenotype results from increased levels of Spo11-catalyzed DSBs in the rDNA.

Authors
Casper, AM; Mieczkowski, PA; Gawel, M; Petes, TD
MLA Citation
Casper, AM, Mieczkowski, PA, Gawel, M, and Petes, TD. "Low levels of DNA polymerase alpha induce mitotic and meiotic instability in the ribosomal DNA gene cluster of Saccharomyces cerevisiae. (Published online)" PLoS Genet 4.6 (June 27, 2008): e1000105-.
PMID
18584028
Source
pubmed
Published In
PLoS genetics
Volume
4
Issue
6
Publish Date
2008
Start Page
e1000105
DOI
10.1371/journal.pgen.1000105

High rates of "unselected" aneuploidy and chromosome rearrangements in tel1 mec1 haploid yeast strains.

The yeast TEL1 and MEC1 genes (homologous to the mammalian ATM and ATR genes, respectively) serve partially redundant roles in the detection of DNA damage and in the regulation of telomere length. Haploid yeast tel1 mec1 strains were subcultured nonselectively for approximately 200 cell divisions. The subcultured strains had very high rates of chromosome aberrations: duplications, deletions, and translocations. The breakpoints of the rearranged chromosomes were within retrotransposons (Ty or delta-repeats), and these chromosome aberrations nonrandomly involved chromosome III. In addition, we showed that strains with the hypomorphic mec1-21 allele often became disomic for chromosome VIII. This property of the mec1-21 strains is suppressed by a plasmid containing the DNA2 gene (located on chromosome VIII) that encodes an essential nuclease/helicase involved in DNA replication and DNA repair.

Authors
Vernon, M; Lobachev, K; Petes, TD
MLA Citation
Vernon, M, Lobachev, K, and Petes, TD. "High rates of "unselected" aneuploidy and chromosome rearrangements in tel1 mec1 haploid yeast strains." Genetics 179.1 (May 2008): 237-247.
PMID
18458104
Source
pubmed
Published In
Genetics
Volume
179
Issue
1
Publish Date
2008
Start Page
237
End Page
247
DOI
10.1534/genetics.107.086603

Role of proliferating cell nuclear antigen interactions in the mismatch repair-dependent processing of mitotic and meiotic recombination intermediates in yeast.

The mismatch repair (MMR) system is critical not only for the repair of DNA replication errors, but also for the regulation of mitotic and meiotic recombination processes. In a manner analogous to its ability to remove replication errors, the MMR system can remove mismatches in heteroduplex recombination intermediates to generate gene conversion events. Alternatively, such mismatches can trigger an MMR-dependent antirecombination activity that blocks the completion of recombination, thereby limiting interactions between diverged sequences. In Saccharomyces cerevisiae, the MMR proteins Msh3, Msh6, and Mlh1 interact with proliferating cell nuclear antigen (PCNA), and mutations that disrupt these interactions result in a mutator phenotype. In addition, some mutations in the PCNA-encoding POL30 gene increase mutation rates in an MMR-dependent manner. In the current study, pol30, mlh1, and msh6 mutants were used to examine whether MMR-PCNA interactions are similarly important during mitotic and meiotic recombination. We find that MMR-PCNA interactions are important for repairing mismatches formed during meiotic recombination, but play only a relatively minor role in regulating the fidelity of mitotic recombination.

Authors
Stone, JE; Ozbirn, RG; Petes, TD; Jinks-Robertson, S
MLA Citation
Stone, JE, Ozbirn, RG, Petes, TD, and Jinks-Robertson, S. "Role of proliferating cell nuclear antigen interactions in the mismatch repair-dependent processing of mitotic and meiotic recombination intermediates in yeast." Genetics 178.3 (March 2008): 1221-1236.
PMID
18245822
Source
pubmed
Published In
Genetics
Volume
178
Issue
3
Publish Date
2008
Start Page
1221
End Page
1236
DOI
10.1534/genetics.107.085415

Ninety-six haploid yeast strains with individual disruptions of open reading frames between YOR097C and YOR192C, constructed for the Saccharomyces genome deletion project, have an additional mutation in the mismatch repair gene MSH3.

As part of the Saccharomyces Genome Deletion Project, sets of presumably isogenic haploid and diploid strains that differed only by single gene deletions were constructed. We found that one set of 96 strains (containing deletions of ORFs located between YOR097C and YOR192C) in the collection, which was derived from the haploid BY4741, has an additional mutation in the MSH3 mismatch repair gene.

Authors
Lehner, KR; Stone, MM; Farber, RA; Petes, TD
MLA Citation
Lehner, KR, Stone, MM, Farber, RA, and Petes, TD. "Ninety-six haploid yeast strains with individual disruptions of open reading frames between YOR097C and YOR192C, constructed for the Saccharomyces genome deletion project, have an additional mutation in the mismatch repair gene MSH3." Genetics 177.3 (November 2007): 1951-1953.
PMID
17947417
Source
pubmed
Published In
Genetics
Volume
177
Issue
3
Publish Date
2007
Start Page
1951
End Page
1953
DOI
10.1534/genetics.107.079368

Inverted DNA repeats channel repair of distant double-strand breaks into chromatid fusions and chromosomal rearrangements.

Inverted DNA repeats are known to cause genomic instabilities. Here we demonstrate that double-strand DNA breaks (DSBs) introduced a large distance from inverted repeats in the yeast (Saccharomyces cerevisiae) chromosome lead to a burst of genomic instability. Inverted repeats located as far as 21 kb from each other caused chromosome rearrangements in response to a single DSB. We demonstrate that the DSB initiates a pairing interaction between inverted repeats, resulting in the formation of large dicentric inverted dimers. Furthermore, we observed that propagation of cells containing inverted dimers led to gross chromosomal rearrangements, including translocations, truncations, and amplifications. Finally, our data suggest that break-induced replication is responsible for the formation of translocations resulting from anaphase breakage of inverted dimers. We propose a model explaining the formation of inverted dicentric dimers by intermolecular single-strand annealing (SSA) between inverted DNA repeats. According to this model, anaphase breakage of inverted dicentric dimers leads to gross chromosomal rearrangements (GCR). This "SSA-GCR" pathway is likely to be important in the repair of isochromatid breaks resulting from collapsed replication forks, certain types of radiation, or telomere aberrations that mimic isochromatid breaks.

Authors
VanHulle, K; Lemoine, FJ; Narayanan, V; Downing, B; Hull, K; McCullough, C; Bellinger, M; Lobachev, K; Petes, TD; Malkova, A
MLA Citation
VanHulle, K, Lemoine, FJ, Narayanan, V, Downing, B, Hull, K, McCullough, C, Bellinger, M, Lobachev, K, Petes, TD, and Malkova, A. "Inverted DNA repeats channel repair of distant double-strand breaks into chromatid fusions and chromosomal rearrangements." Mol Cell Biol 27.7 (April 2007): 2601-2614.
PMID
17242181
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
27
Issue
7
Publish Date
2007
Start Page
2601
End Page
2614
DOI
10.1128/MCB.01740-06

Loss of a histone deacetylase dramatically alters the genomic distribution of Spo11p-catalyzed DNA breaks in Saccharomyces cerevisiae.

In eukaryotes, meiotic recombination events are distributed nonrandomly in the genome, with certain regions having high levels of recombination (hotspots) and others having low levels (coldspots). Species with similar DNA sequences (for example, chimpanzees and humans) can have strikingly different patterns of hotspots and coldspots. Below, by using a microarray analysis that allows us to measure the frequency of the meiosis-specific double-strand DNA breaks (DSBs) of all 6,000 yeast genes, we show that mutation of a single gene (SIR2), which encodes a histone deacetylase, significantly changes DSB frequencies of 12% of yeast genes, elevating DSBs of 5%, and reducing DSBs of 7%. Many of the genes with repressed recombination are located in large (50-100 kb) regions located near, but not at, the telomeres. Some of the genes with altered frequencies of DSBs (including the ribosomal RNA gene cluster) are known targets of Sir2p deacetylation in the wild-type strain.

Authors
Mieczkowski, PA; Dominska, M; Buck, MJ; Lieb, JD; Petes, TD
MLA Citation
Mieczkowski, PA, Dominska, M, Buck, MJ, Lieb, JD, and Petes, TD. "Loss of a histone deacetylase dramatically alters the genomic distribution of Spo11p-catalyzed DNA breaks in Saccharomyces cerevisiae." Proc Natl Acad Sci U S A 104.10 (March 6, 2007): 3955-3960.
PMID
17360459
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
104
Issue
10
Publish Date
2007
Start Page
3955
End Page
3960
DOI
10.1073/pnas.0700412104

Recombination between retrotransposons as a source of chromosome rearrangements in the yeast Saccharomyces cerevisiae.

Homologous recombination between dispersed repeated genetic elements is an important source of genetic variation. In this review, we discuss chromosome rearrangements that are a consequence of homologous recombination between transposable elements in the yeast Saccharomyces cerevisiae. The review will be divided into five sections: (1) Introduction (mechanisms of homologous recombination involving ectopic repeats), (2) Spontaneous chromosome rearrangements in wild-type yeast cells, (3) Chromosome rearrangements induced by low DNA polymerase, mutagenic agents or mutations in genes affecting genome stability, (4) Recombination between retrotransposons as a mechanism of genome evolution, and (5) Important unanswered questions about homologous recombination between retrotransposons. This review complements several others [S. Liebman, S. Picologlou, Recombination associated with yeast retrotransposons, in: Y. Koltin, M.J. Leibowitz (Eds.), Viruses of Fungi and Simple Eukaryotes, Marcel Dekker Inc., New York, 1988, pp. 63-89; P. Lesage, A.L. Todeschini, Happy together: the life and times of Ty retrotransposons and their hosts, Cytogenet. Genome Res. 110 (2005) 70-90; D.J. Garfinkel, Genome evolution mediated by Ty elements in Saccharomyces, Cytogenet. Genome Res. 110 (2005) 63-69] that discuss genomic rearrangements involving Ty elements.

Authors
Mieczkowski, PA; Lemoine, FJ; Petes, TD
MLA Citation
Mieczkowski, PA, Lemoine, FJ, and Petes, TD. "Recombination between retrotransposons as a source of chromosome rearrangements in the yeast Saccharomyces cerevisiae." DNA Repair (Amst) 5.9-10 (September 8, 2006): 1010-1020. (Review)
PMID
16798113
Source
pubmed
Published In
DNA Repair
Volume
5
Issue
9-10
Publish Date
2006
Start Page
1010
End Page
1020
DOI
10.1016/j.dnarep.2006.05.027

Selection and analysis of spontaneous reciprocal mitotic cross-overs in Saccharomyces cerevisiae.

We developed a system that allows the selection of the reciprocal products resulting from spontaneous mitotic cross-overs in the yeast Saccharomyces cerevisiae. A number of other types of genetic events, including chromosome loss, can be monitored with this system. For a 120-kb chromosome interval on chromosome V (CEN5-CAN1), the rate of mitotic cross-overs was 4x10(-5) per division, a rate approximately 25,000-fold lower than the meiotic rate of cross-overs. We found no suppression of mitotic cross-overs near the centromere of chromosome V, unlike the suppression observed for meiotic exchanges. The rate of reciprocal cross-overs was substantially (38-fold) elevated by treatment of cells with hydroxyurea, a drug that reduces nucleotide pools and slows DNA replication.

Authors
Barbera, MA; Petes, TD
MLA Citation
Barbera, MA, and Petes, TD. "Selection and analysis of spontaneous reciprocal mitotic cross-overs in Saccharomyces cerevisiae." Proc Natl Acad Sci U S A 103.34 (August 22, 2006): 12819-12824.
PMID
16908833
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
103
Issue
34
Publish Date
2006
Start Page
12819
End Page
12824
DOI
10.1073/pnas.0605778103

Analysis of the proteins involved in the in vivo repair of base-base mismatches and four-base loops formed during meiotic recombination in the yeast Saccharomyces cerevisiae.

DNA mismatches are generated when heteroduplexes formed during recombination involve DNA strands that are not completely complementary. We used tetrad analysis in Saccharomyces cerevisiae to examine the meiotic repair of a base-base mismatch and a four-base loop in a wild-type strain and in strains with mutations in genes implicated in DNA mismatch repair. Efficient repair of the base-base mismatch required Msh2p, Msh6p, Mlh1p, and Pms1p, but not Msh3p, Msh4p, Msh5p, Mlh2p, Mlh3p, Exo1p, Rad1p, Rad27p, or the DNA proofreading exonuclease of DNA polymerase delta. Efficient repair of the four-base loop required Msh2p, Msh3p, Mlh1p, and Pms1p, but not Msh4p, Msh5p, Msh6p, Mlh2p, Mlh3p, Exo1p, Rad1p, Rad27p, or the proofreading exonuclease of DNA polymerase delta. We find evidence that a novel Mlh1p-independent complex competes with an Mlhp-dependent complex for the repair of a four-base loop; repair of the four-base loop was affected by loss of the Mlh3p, and the repair defect of the mlh1 and pms1 strains was significantly smaller than that observed in the msh2 strain. We also found that the frequency and position of local double-strand DNA breaks affect the ratio of mismatch repair events that lead to gene conversion vs. restoration of Mendelian segregation.

Authors
Stone, JE; Petes, TD
MLA Citation
Stone, JE, and Petes, TD. "Analysis of the proteins involved in the in vivo repair of base-base mismatches and four-base loops formed during meiotic recombination in the yeast Saccharomyces cerevisiae." Genetics 173.3 (July 2006): 1223-1239.
PMID
16702432
Source
pubmed
Published In
Genetics
Volume
173
Issue
3
Publish Date
2006
Start Page
1223
End Page
1239
DOI
10.1534/genetics.106.055616

The pattern of gene amplification is determined by the chromosomal location of hairpin-capped breaks.

DNA palindromes often colocalize in cancer cells with chromosomal regions that are predisposed to gene amplification. The molecular mechanisms by which palindromes can cause gene amplification are largely unknown. Using yeast as a model system, we found that hairpin-capped double-strand breaks (DSBs) occurring at the location of human Alu-quasipalindromes lead to the formation of intrachromosomal amplicons with large inverted repeats (equivalent to homogeneously staining regions in mammalian chromosomes) or extrachromosomal palindromic molecules (equivalent to double minutes [DM] in mammalian cells). We demonstrate that the specific outcomes of gene amplification depend on the applied selection, the nature of the break, and the chromosomal location of the amplified gene relative to the site of the hairpin-capped DSB. The rules for the palindrome-dependent pathway of gene amplification defined in yeast may operate during the formation of amplicons in human tumors.

Authors
Narayanan, V; Mieczkowski, PA; Kim, H-M; Petes, TD; Lobachev, KS
MLA Citation
Narayanan, V, Mieczkowski, PA, Kim, H-M, Petes, TD, and Lobachev, KS. "The pattern of gene amplification is determined by the chromosomal location of hairpin-capped breaks." Cell 125.7 (June 30, 2006): 1283-1296.
PMID
16814715
Source
pubmed
Published In
Cell
Volume
125
Issue
7
Publish Date
2006
Start Page
1283
End Page
1296
DOI
10.1016/j.cell.2006.04.042

Global analysis of the relationship between the binding of the Bas1p transcription factor and meiosis-specific double-strand DNA breaks in Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, certain genomic regions have very high levels of meiotic recombination (hot spots). The hot spot activity associated with the HIS4 gene requires the Bas1p transcription factor. To determine whether this relationship between transcription factor binding and hot spot activity is general, we used DNA microarrays to map all genomic Bas1p binding sites and to map the frequency of meiosis-specific double-strand DNA breaks (as an estimate of the recombination activity) of all genes in both wild-type and bas1 strains. We identified sites of Bas1p-DNA interactions upstream of 71 genes, many of which are involved in histidine and purine biosynthesis. Our analysis of recombination activity in wild-type and bas1 strains showed that the recombination activities of some genes with Bas1p binding sites were dependent on Bas1p (as observed for HIS4), whereas the activities of other genes with Bas1p binding sites were unaffected or were repressed by Bas1p. These data demonstrate that the effect of transcription factors on meiotic recombination activity is strongly context dependent. In wild-type and bas1 strains, meiotic recombination was strongly suppressed in large (25- to 150-kb) chromosomal regions near the telomeres and centromeres and in the region flanking the rRNA genes. These results argue that both local and regional factors affect the level of meiotic recombination.

Authors
Mieczkowski, PA; Dominska, M; Buck, MJ; Gerton, JL; Lieb, JD; Petes, TD
MLA Citation
Mieczkowski, PA, Dominska, M, Buck, MJ, Gerton, JL, Lieb, JD, and Petes, TD. "Global analysis of the relationship between the binding of the Bas1p transcription factor and meiosis-specific double-strand DNA breaks in Saccharomyces cerevisiae." Mol Cell Biol 26.3 (February 2006): 1014-1027.
PMID
16428454
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
26
Issue
3
Publish Date
2006
Start Page
1014
End Page
1027
DOI
10.1128/MCB.26.3.1014-1027.2006

Variation in efficiency of DNA mismatch repair at different sites in the yeast genome.

Evolutionary studies have suggested that mutation rates vary significantly at different positions in the eukaryotic genome. The mechanism that is responsible for this context-dependence of mutation rates is not understood. We demonstrate experimentally that frameshift mutation rates in yeast microsatellites depend on the genomic context and that this variation primarily reflects the context-dependence of the efficiency of DNA mismatch repair. We measured the stability of a 16.5-repeat polyGT tract by using a reporter gene (URA3-GT) in which the microsatellite was inserted in-frame into the yeast URA3 gene. We constructed 10 isogenic yeast strains with the reporter gene at different locations in the genome. Rates of frameshift mutations that abolished the correct reading frame of this gene were determined by fluctuation analysis. A 16-fold difference was found among these strains. We made mismatch-repair-deficient (msh2) derivatives of six of the strains. Mutation rates were elevated for all of these strains, but the differences in rates among the strains were substantially reduced. The simplest interpretation of this result is that the efficiency of DNA mismatch repair varies in different regions of the genome, perhaps reflecting some aspect of chromosome structure.

Authors
Hawk, JD; Stefanovic, L; Boyer, JC; Petes, TD; Farber, RA
MLA Citation
Hawk, JD, Stefanovic, L, Boyer, JC, Petes, TD, and Farber, RA. "Variation in efficiency of DNA mismatch repair at different sites in the yeast genome." Proc Natl Acad Sci U S A 102.24 (June 14, 2005): 8639-8643.
PMID
15932942
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
102
Issue
24
Publish Date
2005
Start Page
8639
End Page
8643
DOI
10.1073/pnas.0503415102

Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites.

In the yeast Saccharomyces cerevisiae, reduced levels of the replicative alpha DNA polymerase result in greatly elevated frequencies of chromosome translocations and chromosome loss. We selected translocations in a small region of chromosome III and found that they involve homologous recombination events between yeast retrotransposons (Ty elements) on chromosome III and retrotransposons located on other chromosomes. One of the two preferred sites of these translocations on chromosome III involve two Ty elements arrayed head-to-head; disruption of this site substantially reduces the rate of translocations. We demonstrate that this pair of Ty elements constitutes a preferred site for double-strand DNA breaks when DNA replication is compromised, analogous to the fragile sites observed in mammalian chromosomes.

Authors
Lemoine, FJ; Degtyareva, NP; Lobachev, K; Petes, TD
MLA Citation
Lemoine, FJ, Degtyareva, NP, Lobachev, K, and Petes, TD. "Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites." Cell 120.5 (March 11, 2005): 587-598.
PMID
15766523
Source
pubmed
Published In
Cell
Volume
120
Issue
5
Publish Date
2005
Start Page
587
End Page
598
DOI
10.1016/j.cell.2004.12.039

Inositol diphosphate signaling regulates telomere length.

Activation of phospholipase C-dependent inositol polyphosphate signaling pathways generates distinct messengers derived from inositol 1,4,5-trisphosphate that control gene expression and mRNA export. Here we report the regulation of telomere length by production of a diphosphorylinositol tetrakisphosphate, PP-IP4, synthesized by the KCS1 gene product. Loss of PP-IP4 production results in lengthening of telomeres, whereas overproduction leads to their shortening. This effect requires the presence of Tel1, the yeast homologue of ATM, the protein mutated in the human disease ataxia telangiectasia. Our data provide in vivo evidence of a regulatory link between inositol polyphosphate signaling and the checkpoint kinase family and describe a third nuclear process modulated by phospholipase C activation.

Authors
York, SJ; Armbruster, BN; Greenwell, P; Petes, TD; York, JD
MLA Citation
York, SJ, Armbruster, BN, Greenwell, P, Petes, TD, and York, JD. "Inositol diphosphate signaling regulates telomere length." J Biol Chem 280.6 (February 11, 2005): 4264-4269.
PMID
15561716
Source
pubmed
Published In
The Journal of biological chemistry
Volume
280
Issue
6
Publish Date
2005
Start Page
4264
End Page
4269
DOI
10.1074/jbc.M412070200

The compact chromatin structure of a Ty repeated sequence suppresses recombination hotspot activity in Saccharomyces cerevisiae.

Recombination between repeated DNA sequences can have drastic consequences on the integrity of the genome. Repeated sequences are abundant in most eukaryotes, yet the mechanism that prevents recombination between them is currently unknown. Ty elements, the main family of dispersed repeats in Saccharomyces cerevisiae, exhibit low levels of exchange. Other regions in the genome have relatively high rates of meiotic recombination (hotspots). We show that a Ty element adjacent to the HIS4 recombination hotspot substantially reduces its activity, eliminating local DSB formation. We demonstrate that the Ty has a closed (nuclease-insensitive) chromatin configuration that is also imposed on the flanking DNA sequences. The compact chromatin structure is determined by sequences at the N terminus of the Ty. Increased binding of the Rap1 protein to the hotspot restores both open chromatin conformation and DSB formation. The chromatin configuration of Ty elements precludes initiation of recombination, thus preventing potentially lethal exchanges between repeated sequences.

Authors
Ben-Aroya, S; Mieczkowski, PA; Petes, TD; Kupiec, M
MLA Citation
Ben-Aroya, S, Mieczkowski, PA, Petes, TD, and Kupiec, M. "The compact chromatin structure of a Ty repeated sequence suppresses recombination hotspot activity in Saccharomyces cerevisiae." Mol Cell 15.2 (July 23, 2004): 221-231.
PMID
15260973
Source
pubmed
Published In
Molecular Cell
Volume
15
Issue
2
Publish Date
2004
Start Page
221
End Page
231
DOI
10.1016/j.molcel.2004.06.002

Amino acid changes in Xrs2p, Dun1p, and Rfa2p that remove the preferred targets of the ATM family of protein kinases do not affect DNA repair or telomere length in Saccharomyces cerevisiae.

In eukaryotes, mutations in a number of genes that affect DNA damage checkpoints or DNA replication also affect telomere length [Curr. Opin. Cell Biol. 13 (2001) 281]. Saccharomyces cerevisae strains with mutations in the TEL1 gene (encoding an ATM-like protein kinase) have very short telomeres, as do strains with mutations in XRS2, RAD50, or MRE11 (encoding members of a trimeric complex). Xrs2p and Mre11p are phosphorylated in a Tel1p-dependent manner in response to DNA damage [Genes Dev. 15 (2001) 2238; Mol. Cell 7 (2001) 1255]. We found that Xrs2p, but not Mre11p or Rad50p, is efficiently phosphorylated in vitro by immunopreciptated Tel1p. Strains with mutations eliminating all SQ and TQ motifs in Xrs2p (preferred targets of the ATM kinase family) had wild-type length telomeres and wild-type sensitivity to DNA damaging agents. We also showed that Rfa2p (a subunit of RPA) and the Dun1p checkpoint kinase, which are required for DNA damage repair and which are phosphorylated in response to DNA damage in vivo, are in vitro substrates of the Tel1p and Mec1p kinases. In addition, Dun1p substrates with no SQ or TQ motifs are phosphorylated by Mec1p in vitro very inefficiently, but retain most of their ability to be phosphorylated by Tel1p. We demonstrated that null alleles of DUN1 and certain mutant alleles of RFA2 result in short telomeres. As observed with Xrs2p, however, strains with mutations of DUN1 or RFA2 that eliminate SQ motifs have no effect on telomere length or DNA damage sensitivity.

Authors
Mallory, JC; Bashkirov, VI; Trujillo, KM; Solinger, JA; Dominska, M; Sung, P; Heyer, WD; Petes, TD
MLA Citation
Mallory, JC, Bashkirov, VI, Trujillo, KM, Solinger, JA, Dominska, M, Sung, P, Heyer, WD, and Petes, TD. "Amino acid changes in Xrs2p, Dun1p, and Rfa2p that remove the preferred targets of the ATM family of protein kinases do not affect DNA repair or telomere length in Saccharomyces cerevisiae." DNA Repair (Amst) 2.9 (September 18, 2003): 1041-1064.
PMID
12967660
Source
pubmed
Published In
DNA Repair
Volume
2
Issue
9
Publish Date
2003
Start Page
1041
End Page
1064

Genetic regulation of telomere-telomere fusions in the yeast Saccharomyces cerevisae.

Yeast strains with mutations in both TEL1 and MEC1 have short telomeres and elevated rates of chromosome deletions. By using a PCR assay, we demonstrate that mec1 tel1 strains also have telomere-telomere fusions (T-TFs). T-TFs require Lig4p (a ligase required for nonhomologous end-joining DNA repair). The highest rates of T-TFs are found in strains with combination of mutations that affect telomere length and DNA damage checkpoints (mec1 tel1, mec3 tel1, mre11 mec1, and ddc1 tel1 strains). Examining many mutant genotypes, we find good agreement between the level of T-TFs and the rate of chromosomal deletions. In addition, if telomeres are elongated in a mec1 tel1 strain, we eliminate T-TFs and reduce the deletion rate. The correlation between the level of T-TFs and the rate of deletions argues that many of these deletions reflect a cycle of T-TF formation (resulting in dicentric chromosomes), followed by chromosome breakage.

Authors
Mieczkowski, PA; Mieczkowska, JO; Dominska, M; Petes, TD
MLA Citation
Mieczkowski, PA, Mieczkowska, JO, Dominska, M, and Petes, TD. "Genetic regulation of telomere-telomere fusions in the yeast Saccharomyces cerevisae." Proc Natl Acad Sci U S A 100.19 (September 16, 2003): 10854-10859.
PMID
12963812
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
100
Issue
19
Publish Date
2003
Start Page
10854
End Page
10859
DOI
10.1073/pnas.1934561100

Patterns of heteroduplex formation associated with the initiation of meiotic recombination in the yeast Saccharomyces cerevisiae.

The double-strand break repair (DSBR) model of recombination predicts that heteroduplexes will be formed in regions that flank the double-strand break (DSB) site and that the resulting intermediate is resolved to generate either crossovers or noncrossovers for flanking markers. Previous studies in Saccharomyces cerevisiae, however, failed to detect heteroduplexes on both sides of the DSB site. Recent physical studies suggest that some recombination events involve heterodupex formation by a mechanism, synthesis-dependent strand annealing (SDSA), that is inherently asymmetric with respect to the DSB site and that leads exclusively to noncrossovers of flanking markers. Below, we demonstrate that many of the recombination events initiated at the HIS4 recombination hotspot are consistent with a variant of the DSBR model in which the extent of heteroduplex on one side of the DSB site is much greater than that on the other. Events that include only one flanking marker in the heteroduplex (unidirectional events) are usually resolved as noncrossovers, whereas events that include both flanking markers (bidirectional events) are usually resolved as crossovers. The unidirectional events may represent SDSA, consistent with the conclusions of others, although other possibilities are not excluded. We also show that the level of recombination reflects the integration of events initiated at several different DSB sites, and we identify a subset of gene conversion events that may involve break-induced replication (BIR) or repair of a double-stranded DNA gap.

Authors
Merker, JD; Dominska, M; Petes, TD
MLA Citation
Merker, JD, Dominska, M, and Petes, TD. "Patterns of heteroduplex formation associated with the initiation of meiotic recombination in the yeast Saccharomyces cerevisiae." Genetics 165.1 (September 2003): 47-63.
PMID
14504217
Source
pubmed
Published In
Genetics
Volume
165
Issue
1
Publish Date
2003
Start Page
47
End Page
63

Context dependence of meiotic recombination hotspots in yeast: the relationship between recombination activity of a reporter construct and base composition.

Borde and colleagues reported that a reporter plasmid inserted at different genomic locations in Saccharomyces cerevisiae had different levels of meiotic recombination activity. We show that the level of recombination activity is very significantly correlated with the GC content of DNA sequences flanking the insertion.

Authors
Petes, TD; Merker, JD
MLA Citation
Petes, TD, and Merker, JD. "Context dependence of meiotic recombination hotspots in yeast: the relationship between recombination activity of a reporter construct and base composition." Genetics 162.4 (December 2002): 2049-2052.
PMID
12524370
Source
pubmed
Published In
Genetics
Volume
162
Issue
4
Publish Date
2002
Start Page
2049
End Page
2052

Alleles of the yeast Pms1 mismatch-repair gene that differentially affect recombination- and replication-related processes.

Mismatch-repair (MMR) systems promote eukaryotic genome stability by removing errors introduced during DNA replication and by inhibiting recombination between nonidentical sequences (spellchecker and antirecombination activities, respectively). Following a common mismatch-recognition step effected by MutS-homologous Msh proteins, homologs of the bacterial MutL ATPase (predominantly the Mlh1p-Pms1p heterodimer in yeast) couple mismatch recognition to the appropriate downstream processing steps. To examine whether the processing steps in the spellchecker and antirecombination pathways might differ, we mutagenized the yeast PMS1 gene and screened for mitotic separation-of-function alleles. Two alleles affecting only the antirecombination function of Pms1p were identified, one of which changed an amino acid within the highly conserved ATPase domain. To more specifically address the role of ATP binding/hydrolysis in MMR-related processes, we examined mutations known to compromise the ATPase activity of Pms1p or Mlh1p with respect to the mitotic spellchecker and antirecombination activities and with respect to the repair of mismatches present in meiotic recombination intermediates. The results of these analyses confirm a differential requirement for the Pms1p ATPase activity in replication vs. recombination processes, while demonstrating that the Mlh1p ATPase activity is important for all examined MMR-related functions.

Authors
Welz-Voegele, C; Stone, JE; Tran, PT; Kearney, HM; Liskay, RM; Petes, TD; Jinks-Robertson, S
MLA Citation
Welz-Voegele, C, Stone, JE, Tran, PT, Kearney, HM, Liskay, RM, Petes, TD, and Jinks-Robertson, S. "Alleles of the yeast Pms1 mismatch-repair gene that differentially affect recombination- and replication-related processes." Genetics 162.3 (November 2002): 1131-1145.
PMID
12454061
Source
pubmed
Published In
Genetics
Volume
162
Issue
3
Publish Date
2002
Start Page
1131
End Page
1145

Regulation of genome stability by TEL1 and MEC1, yeast homologs of the mammalian ATM and ATR genes.

In eukaryotes, a family of related protein kinases (the ATM family) is involved in regulating cellular responses to DNA damage and telomere length. In the yeast Saccharomyces cerevisiae, two members of this family, TEL1 and MEC1, have functionally redundant roles in both DNA damage repair and telomere length regulation. Strains with mutations in both genes are very sensitive to DNA damaging agents, have very short telomeres, and undergo cellular senescence. We find that strains with the double mutant genotype also have approximately 80-fold increased rates of mitotic recombination and chromosome loss. In addition, the tel1 mec1 strains have high rates of telomeric fusions, resulting in translocations, dicentrics, and circular chromosomes. Similar chromosome rearrangements have been detected in mammalian cells with mutations in ATM (related to TEL1) and ATR (related to MEC1) and in mammalian cells that approach cell crisis.

Authors
Craven, RJ; Greenwell, PW; Dominska, M; Petes, TD
MLA Citation
Craven, RJ, Greenwell, PW, Dominska, M, and Petes, TD. "Regulation of genome stability by TEL1 and MEC1, yeast homologs of the mammalian ATM and ATR genes." Genetics 161.2 (June 2002): 493-507.
PMID
12072449
Source
pubmed
Published In
Genetics
Volume
161
Issue
2
Publish Date
2002
Start Page
493
End Page
507

Caenorhabditis elegans DNA mismatch repair gene msh-2 is required for microsatellite stability and maintenance of genome integrity.

Mismatch repair genes are important in maintaining the fidelity of DNA replication. To determine the function of the Caenorhabditis elegans homologue of the MSH2 mismatch repair gene (msh-2), we isolated a strain of C. elegans with an insertion of the transposable element Tc1 within msh-2. Early-passage msh-2 mutants were similar to wild-type worms with regard to lifespan and meiotic chromosome segregation but had slightly reduced fertility. The mutant worms had reduced DNA damage-induced germ-line apoptosis after genotoxic stress. The msh-2 mutants also had elevated levels of microsatellite instability and increased rates of reversion of the dominant unc-58(e665) mutation. In addition, serially passaged cultures of msh-2 worms died out much more quickly than those of wild-type worms. These results demonstrate that msh-2 function in C. elegans is important in regulating both short- and long-term genomic stability.

Authors
Degtyareva, NP; Greenwell, P; Hofmann, ER; Hengartner, MO; Zhang, L; Culotti, JG; Petes, TD
MLA Citation
Degtyareva, NP, Greenwell, P, Hofmann, ER, Hengartner, MO, Zhang, L, Culotti, JG, and Petes, TD. "Caenorhabditis elegans DNA mismatch repair gene msh-2 is required for microsatellite stability and maintenance of genome integrity." Proc Natl Acad Sci U S A 99.4 (February 19, 2002): 2158-2163.
PMID
11830642
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
99
Issue
4
Publish Date
2002
Start Page
2158
End Page
2163
DOI
10.1073/pnas.032671599

Isolation and characterization of point mutations in mismatch repair genes that destabilize microsatellites in yeast.

The stability of simple repetitive DNA sequences (microsatellites) is a sensitive indicator of the ability of a cell to repair DNA mismatches. In a genetic screen for yeast mutants with elevated microsatellite instability, we identified strains containing point mutations in the yeast mismatch repair genes, MSH2, MSH3, MLH1, and PMS1. Some of these mutations conferred phenotypes significantly different from those of null mutations in these genes. One semidominant MSH2 mutation was identified. Finally we showed that strains heterozygous for null mutations of mismatch repair genes in diploid strains in yeast confer subtle defects in the repair of small DNA loops.

Authors
Sia, EA; Dominska, M; Stefanovic, L; Petes, TD
MLA Citation
Sia, EA, Dominska, M, Stefanovic, L, and Petes, TD. "Isolation and characterization of point mutations in mismatch repair genes that destabilize microsatellites in yeast." Mol Cell Biol 21.23 (December 2001): 8157-8167.
PMID
11689704
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
21
Issue
23
Publish Date
2001
Start Page
8157
End Page
8167
DOI
10.1128/MCB.21.23.8157-8167.2001

Meiotic recombination involving heterozygous large insertions in Saccharomyces cerevisiae: formation and repair of large, unpaired DNA loops.

Meiotic recombination in Saccharomyces cerevisiae involves the formation of heteroduplexes, duplexes containing DNA strands derived from two different homologues. If the two strands of DNA differ by an insertion or deletion, the heteroduplex will contain an unpaired DNA loop. We found that unpaired loops as large as 5.6 kb can be accommodated within a heteroduplex. Repair of these loops involved the nucleotide excision repair (NER) enzymes Rad1p and Rad10p and the mismatch repair (MMR) proteins Msh2p and Msh3p, but not several other NER (Rad2p and Rad14p) and MMR (Msh4p, Msh6p, Mlh1p, Pms1p, Mlh2p, Mlh3p) proteins. Heteroduplexes were also formed with DNA strands derived from alleles containing two different large insertions, creating a large "bubble"; repair of this substrate was dependent on Rad1p. Although meiotic recombination events in yeast are initiated by double-strand DNA breaks (DSBs), we showed that DSBs occurring within heterozygous insertions do not stimulate interhomologue recombination.

Authors
Kearney, HM; Kirkpatrick, DT; Gerton, JL; Petes, TD
MLA Citation
Kearney, HM, Kirkpatrick, DT, Gerton, JL, and Petes, TD. "Meiotic recombination involving heterozygous large insertions in Saccharomyces cerevisiae: formation and repair of large, unpaired DNA loops." Genetics 158.4 (August 2001): 1457-1476.
PMID
11514439
Source
pubmed
Published In
Genetics
Volume
158
Issue
4
Publish Date
2001
Start Page
1457
End Page
1476

Meiotic recombination hot spots and cold spots.

Meiotic recombination events are distributed unevenly throughout eukaryotic genomes. This inhomogeneity leads to distortions of genetic maps that can hinder the ability of geneticists to identify genes by map-based techniques. Various lines of evidence, particularly from studies of yeast, indicate that the distribution of recombination events might reflect, at least in part, global features of chromosome structure, such as the distribution of modified nucleosomes.

Authors
Petes, TD
MLA Citation
Petes, TD. "Meiotic recombination hot spots and cold spots." Nat Rev Genet 2.5 (May 2001): 360-369. (Review)
PMID
11331902
Source
pubmed
Published In
Nature Reviews Genetics
Volume
2
Issue
5
Publish Date
2001
Start Page
360
End Page
369
DOI
10.1038/35072078

The Saccharomyces cerevisiae suppressor of choline sensitivity (SCS2) gene is a multicopy Suppressor of mec1 telomeric silencing defects.

Mec1p is a cell cycle checkpoint protein related to the ATM protein kinase family. Certain mec1 mutations or overexpression of Mec1p lead to shortened telomeres and loss of telomeric silencing. We conducted a multicopy suppressor screen for genes that suppress the loss of silencing in strains overexpressing Mec1p. We identified SCS2 (suppressor of choline sensitivity), a gene previously isolated as a suppressor of defects in inositol synthesis. Deletion of SCS2 resulted in decreased telomeric silencing, and the scs2 mutation increased the rate of cellular senescence observed for mec1-21 tel1 double mutant cells. Genetic analysis revealed that Scs2p probably acts through a different telomeric silencing pathway from that affected by Mec1p.

Authors
Craven, RJ; Petes, TD
MLA Citation
Craven, RJ, and Petes, TD. "The Saccharomyces cerevisiae suppressor of choline sensitivity (SCS2) gene is a multicopy Suppressor of mec1 telomeric silencing defects." Genetics 158.1 (May 2001): 145-154.
PMID
11333225
Source
pubmed
Published In
Genetics
Volume
158
Issue
1
Publish Date
2001
Start Page
145
End Page
154

Identification of a mutant DNA polymerase delta in Saccharomyces cerevisiae with an antimutator phenotype for frameshift mutations.

We propose that a beta-turn-beta structure, which plays a critical role in exonucleolytic proofreading in the bacteriophage T4 DNA polymerase, is also present in the Saccharomyces cerevisiae DNA pol delta. Site-directed mutagenesis was used to test this proposal by introducing a mutation into the yeast POL3 gene in the region that encodes the putative beta-turn-beta structure. The mutant DNA pol delta has a serine substitution in place of glycine at position 447. DNA replication fidelity of the G447S-DNA pol delta was determined in vivo by using reversion and forward assays. An antimutator phenotype for frameshift mutations in short homopolymeric tracts was observed for the G447S-DNA pol delta in the absence of postreplication mismatch repair, which was produced by inactivation of the MSH2 gene. Because the G447S substitution reduced frameshift but not base substitution mutagenesis, some aspect of DNA polymerase proofreading appears to contribute to production of frameshifts. Possible roles of DNA polymerase proofreading in frameshift mutagenesis are discussed.

Authors
Hadjimarcou, MI; Kokoska, RJ; Petes, TD; Reha-Krantz, LJ
MLA Citation
Hadjimarcou, MI, Kokoska, RJ, Petes, TD, and Reha-Krantz, LJ. "Identification of a mutant DNA polymerase delta in Saccharomyces cerevisiae with an antimutator phenotype for frameshift mutations." Genetics 158.1 (May 2001): 177-186.
PMID
11333228
Source
pubmed
Published In
Genetics
Volume
158
Issue
1
Publish Date
2001
Start Page
177
End Page
186

Decreased meiotic intergenic recombination and increased meiosis I nondisjunction in exo1 mutants of Saccharomyces cerevisiae (vol 156, pg 1549, 2000)

Authors
Kirkpatrick, DT; Ferguson, JR; Petes, TD; Symington, LS
MLA Citation
Kirkpatrick, DT, Ferguson, JR, Petes, TD, and Symington, LS. "Decreased meiotic intergenic recombination and increased meiosis I nondisjunction in exo1 mutants of Saccharomyces cerevisiae (vol 156, pg 1549, 2000)." GENETICS 157.3 (March 2001): 1397-1397.
Source
wos-lite
Published In
Genetics
Volume
157
Issue
3
Publish Date
2001
Start Page
1397
End Page
1397

Erratum: Decreased meiotic intergenic recombination and increased meiosis I nondisjunction in exo1 mutants of saccharomyces cerevisiae (Genetics 156 (1549-1557))

Authors
Kirkpatrick, DT; Ferguson, JR; Petes, TD; Symington, LS
MLA Citation
Kirkpatrick, DT, Ferguson, JR, Petes, TD, and Symington, LS. "Erratum: Decreased meiotic intergenic recombination and increased meiosis I nondisjunction in exo1 mutants of saccharomyces cerevisiae (Genetics 156 (1549-1557))." Genetics 157.3 (2001): 1397--.
Source
scival
Published In
Genetics
Volume
157
Issue
3
Publish Date
2001
Start Page
1397-

Protein kinase activity of Tel1p and Mec1p, two Saccharomyces cerevisiae proteins related to the human ATM protein kinase.

The Saccharomyces cerevisiae proteins Tel1p and Mec1p are involved in telomere length regulation and cellular responses to DNA damage. The closest relative of these proteins is the human Ataxia Telangiectasia Mutated (ATM) protein, a wortmannin-sensitive protein kinase that primarily phosphorylates serines in an SQ motif. We constructed yeast strains containing functional epitope-tagged versions of Tel1p and Mec1p. We showed that immunoprecipitated Tel1p and Mec1p were capable of in vitro phosphorylation of the mammalian protein PHAS-I (Phosphorylated Heat and Acid Stable protein). These activities are sensitive to wortmannin. Tel1p phosphorylates serine in an SQ motif in PHAS-I. Mutations in the kinase domains of Tel1p and Mec1p result in loss of in vitro kinase activity and the in vivo phenotypes associated with the null tel1 and mec1 mutations.

Authors
Mallory, JC; Petes, TD
MLA Citation
Mallory, JC, and Petes, TD. "Protein kinase activity of Tel1p and Mec1p, two Saccharomyces cerevisiae proteins related to the human ATM protein kinase." Proc Natl Acad Sci U S A 97.25 (December 5, 2000): 13749-13754.
PMID
11095737
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
97
Issue
25
Publish Date
2000
Start Page
13749
End Page
13754
DOI
10.1073/pnas.250475697

Decreased meiotic intergenic recombination and increased meiosis I nondisjunction in exo1 mutants of Saccharomyces cerevisiae.

Exonuclease I was originally identified as a 5' --> 3' deoxyribonuclease present in fractionated extracts of Schizosaccharomyces pombe and Saccharomyces cerevisiae. Genetic analysis of exo1 mutants of both yeasts revealed no major defect in meiosis, suggesting that exonuclease I is unlikely to be the primary activity that processes meiosis-specific double-strand breaks (DSBs). We report here that exo1 mutants of S. cerevisiae exhibit subtle but complex defects in meiosis. Diploids containing a homozygous deletion of EXO1 show decreased spore viability associated with an increase in meiosis I nondisjunction, while intergenic recombination is reduced about twofold. Exo1p functions in the same pathway as Msh5p for intergenic recombination. The length of heteroduplex tracts within the HIS4 gene is unaffected by the exo1 mutation. These results suggest that Exo1p is unlikely to play a major role in processing DSBs to form single-stranded tails at HIS4, but instead appears to promote crossing over to ensure disjunction of homologous chromosomes. In addition, our data indicate that exonuclease I may have a minor role in the correction of large DNA mismatches that occur in heteroduplex DNA during meiotic recombination at the HIS4 locus.

Authors
Kirkpatrick, DT; Ferguson, JR; Petes, TD; Symington, LS
MLA Citation
Kirkpatrick, DT, Ferguson, JR, Petes, TD, and Symington, LS. "Decreased meiotic intergenic recombination and increased meiosis I nondisjunction in exo1 mutants of Saccharomyces cerevisiae." Genetics 156.4 (December 2000): 1549-1557.
PMID
11102356
Source
pubmed
Published In
Genetics
Volume
156
Issue
4
Publish Date
2000
Start Page
1549
End Page
1557

Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, meiotic recombination is initiated by double-strand DNA breaks (DSBs). Meiotic DSBs occur at relatively high frequencies in some genomic regions (hotspots) and relatively low frequencies in others (coldspots). We used DNA microarrays to estimate variation in the level of nearby meiotic DSBs for all 6,200 yeast genes. Hotspots were nonrandomly associated with regions of high G + C base composition and certain transcriptional profiles. Coldspots were nonrandomly associated with the centromeres and telomeres.

Authors
Gerton, JL; DeRisi, J; Shroff, R; Lichten, M; Brown, PO; Petes, TD
MLA Citation
Gerton, JL, DeRisi, J, Shroff, R, Lichten, M, Brown, PO, and Petes, TD. "Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae." Proc Natl Acad Sci U S A 97.21 (October 10, 2000): 11383-11390.
PMID
11027339
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
97
Issue
21
Publish Date
2000
Start Page
11383
End Page
11390
DOI
10.1073/pnas.97.21.11383

Increased rates of genomic deletions generated by mutations in the yeast gene encoding DNA polymerase delta or by decreases in the cellular levels of DNA polymerase delta.

In Saccharomyces cerevisiae, POL3 encodes the catalytic subunit of DNA polymerase delta. While yeast POL3 mutant strains that lack the proofreading exonuclease activity of the polymerase have a strong mutator phenotype, little is known regarding the role of other Pol3p domains in mutation avoidance. We identified a number of pol3 mutations in regions outside of the exonuclease domain that have a mutator phenotype, substantially elevating the frequency of deletions. These deletions appear to reflect an increased frequency of DNA polymerase slippage. In addition, we demonstrate that reduction in the level of wild-type DNA polymerase results in a similar mutator phenotype. Lowered levels of DNA polymerase also result in increased sensitivity to the DNA-damaging agent methyl methane sulfonate. We conclude that both the quantity and the quality of DNA polymerase delta is important in ensuring genome stability.

Authors
Kokoska, RJ; Stefanovic, L; DeMai, J; Petes, TD
MLA Citation
Kokoska, RJ, Stefanovic, L, DeMai, J, and Petes, TD. "Increased rates of genomic deletions generated by mutations in the yeast gene encoding DNA polymerase delta or by decreases in the cellular levels of DNA polymerase delta." Mol Cell Biol 20.20 (October 2000): 7490-7504.
PMID
11003646
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
20
Issue
20
Publish Date
2000
Start Page
7490
End Page
7504

The Mre11p/Rad50p/Xrs2p complex and the Tel1p function in a single pathway for telomere maintenance in yeast.

The Mre11p/Rad50p/Xrs2p complex is involved in the repair of double-strand DNA breaks, nonhomologous end joining, and telomere length regulation. TEL1 is primarily involved in telomere length regulation. By an epistasis analysis, we conclude that Tel1p and the Mre11p/Rad50p/Xrs2p complex function in a single pathway of telomere length regulation.

Authors
Ritchie, KB; Petes, TD
MLA Citation
Ritchie, KB, and Petes, TD. "The Mre11p/Rad50p/Xrs2p complex and the Tel1p function in a single pathway for telomere maintenance in yeast." Genetics 155.1 (May 2000): 475-479.
PMID
10790418
Source
pubmed
Published In
Genetics
Volume
155
Issue
1
Publish Date
2000
Start Page
475
End Page
479

Involvement of the checkpoint protein Mec1p in silencing of gene expression at telomeres in Saccharomyces cerevisiae.

Yeast strains with a mutation in the MEC1 gene are deficient in the cellular checkpoint response to DNA-damaging agents and have short telomeres (K. B. Ritchie, J. C. Mallory, and T. D. Petes, Mol. Cell. Biol. 19:6065-6075, 1999; T. A. Weinert, G. L. Kiser, and L. H. Hartwell, Genes Dev. 8:652-665, 1994). In wild-type yeast cells, genes inserted near the telomeres are transcriptionally silenced (D. E. Gottschling, O. M. Aparichio, B. L. Billington, and V. A. Zakian, Cell 63:751-762, 1990). We show that mec1 strains have reduced ability to silence gene expression near the telomere. This deficiency was alleviated by the sml1 mutation. Overexpression of Mec1p also resulted in a silencing defect, although this overexpression did not affect the checkpoint function of Mec1p. Telomeric silencing was not affected by mutations in several other genes in the Mec1p checkpoint pathway (null mutations in RAD9 and CHK1 or in several hypomorphic rad53 alleles) but was reduced by a null mutation of DUN1. In addition, the loss of telomeric silencing in mec1 strains was not a consequence of the slightly shortened telomeres observed in these strains.

Authors
Craven, RJ; Petes, TD
MLA Citation
Craven, RJ, and Petes, TD. "Involvement of the checkpoint protein Mec1p in silencing of gene expression at telomeres in Saccharomyces cerevisiae." Mol Cell Biol 20.7 (April 2000): 2378-2384.
PMID
10713162
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
20
Issue
7
Publish Date
2000
Start Page
2378
End Page
2384

Analysis of microsatellite mutations in the mitochondrial DNA of Saccharomyces cerevisiae.

In the nuclear genome of Saccharomyces cerevisiae, simple, repetitive DNA sequences (microsatellites) mutate at rates much higher than nonrepetitive sequences. Most of these mutations are deletions or additions of repeat units. The yeast mitochondrial genome also contains many microsatellites. To examine the stability of these sequences, we constructed a reporter gene (arg8(m)) containing out-of-frame insertions of either poly(AT) or poly(GT) tracts within the coding sequence. Yeast strains with this reporter gene inserted within the mitochondrial genome were constructed. Using these strains, we showed that poly(GT) tracts were considerably less stable than poly(AT) tracts and that alterations usually involved deletions rather than additions of repeat units. In contrast, in the nuclear genome, poly(GT) and poly(AT) tracts had similar stabilities, and alterations usually involved additions rather than deletions. Poly(GT) tracts were more stable in the mitochondria of diploid cells than in haploids. In addition, an msh1 mutation destabilized poly(GT) tracts in the mitochondrial genome.

Authors
Sia, EA; Butler, CA; Dominska, M; Greenwell, P; Fox, TD; Petes, TD
MLA Citation
Sia, EA, Butler, CA, Dominska, M, Greenwell, P, Fox, TD, and Petes, TD. "Analysis of microsatellite mutations in the mitochondrial DNA of Saccharomyces cerevisiae." Proc Natl Acad Sci U S A 97.1 (January 4, 2000): 250-255.
PMID
10618404
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
97
Issue
1
Publish Date
2000
Start Page
250
End Page
255

The yeast HSM3 gene is not involved in DNA mismatch repair in rapidly dividing cells.

Authors
Merker, JD; Datta, A; Kolodner, RD; Petes, TD
MLA Citation
Merker, JD, Datta, A, Kolodner, RD, and Petes, TD. "The yeast HSM3 gene is not involved in DNA mismatch repair in rapidly dividing cells." Genetics 154.1 (January 2000): 491-493. (Letter)
PMID
10681182
Source
pubmed
Published In
Genetics
Volume
154
Issue
1
Publish Date
2000
Start Page
491
End Page
493

Control of meiotic recombination and gene expression in yeast by a simple repetitive DNA sequence that excludes nucleosomes.

Tandem repeats of the pentanucleotide 5'-CCGNN (where N indicates any base) were previously shown to exclude nucleosomes in vitro (Y. -H. Wang and J. D. Griffith, Proc. Natl. Acad. Sci. USA 93:8863-8867, 1996). To determine the in vivo effects of these sequences, we replaced the upstream regulatory sequences of the HIS4 gene of Saccharomyces cerevisiae with either 12 or 48 tandem copies of CCGNN. Both tracts activated HIS4 transcription. We found that (CCGNN)(12) tracts elevated meiotic recombination (hot spot activity), whereas the (CCGNN)(48) tract repressed recombination (cold spot activity). In addition, a "pure" tract of (CCGAT)(12) activated both transcription and meiotic recombination. We suggest that the cold spot activity of the (CCGNN)(48) tract is related to the phenomenon of the suppressive interactions of adjacent hot spots previously described in yeast (Q.-Q. Fan, F. Xu, and T. D. Petes, Mol. Cell. Biol. 15:1679-1688, 1995; Q.-Q. Fan, F. Xu, M. A. White, and T. D. Petes, Genetics 145:661-670, 1997; T.-C. Wu and M. Lichten, Genetics 140:55-66, 1995; L. Xu and N. Kleckner, EMBO J. 16:5115-5128, 1995).

Authors
Kirkpatrick, DT; Wang, YH; Dominska, M; Griffith, JD; Petes, TD
MLA Citation
Kirkpatrick, DT, Wang, YH, Dominska, M, Griffith, JD, and Petes, TD. "Control of meiotic recombination and gene expression in yeast by a simple repetitive DNA sequence that excludes nucleosomes." Mol Cell Biol 19.11 (November 1999): 7661-7671.
PMID
10523654
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
19
Issue
11
Publish Date
1999
Start Page
7661
End Page
7671

Interactions of TLC1 (which encodes the RNA subunit of telomerase), TEL1, and MEC1 in regulating telomere length in the yeast Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, chromosomes terminate with a repetitive sequence [poly(TG(1-3))] 350 to 500 bp in length. Strains with a mutation of TEL1, a homolog of the human gene (ATM) mutated in patients with ataxia telangiectasia, have short but stable telomeric repeats. Mutations of TLC1 (encoding the RNA subunit of telomerase) result in strains that have continually shortening telomeres and a gradual loss of cell viability; survivors of senescence arise as a consequence of a Rad52p-dependent recombination events that amplify telomeric and subtelomeric repeats. We show that a mutation in MEC1 (a gene related in sequence to TEL1 and ATM) reduces telomere length and that tel1 mec1 double mutant strains have a senescent phenotype similar to that found in tlc1 strains. As observed in tlc1 strains, survivors of senescence in the tel1 mec1 strains occur by a Rad52p-dependent amplification of telomeric and subtelomeric repeats. In addition, we find that strains with both tel1 and tlc1 mutations have a delayed loss of cell viability compared to strains with the single tlc1 mutation. This result argues that the role of Tel1p in telomere maintenance is not solely a direct activation of telomerase.

Authors
Ritchie, KB; Mallory, JC; Petes, TD
MLA Citation
Ritchie, KB, Mallory, JC, and Petes, TD. "Interactions of TLC1 (which encodes the RNA subunit of telomerase), TEL1, and MEC1 in regulating telomere length in the yeast Saccharomyces cerevisiae." Mol Cell Biol 19.9 (September 1999): 6065-6075.
PMID
10454554
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
19
Issue
9
Publish Date
1999
Start Page
6065
End Page
6075

Dependence of the regulation of telomere length on the type of subtelomeric repeat in the yeast Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, chromosomes terminate with approximately 400 bp of a simple repeat poly(TG(1-3)). Based on the arrangement of subtelomeric X and Y' repeats, two types of yeast telomeres exist, those with both X and Y' (Y' telomeres) and those with only X (X telomeres). Mutations that result in abnormally short or abnormally long poly(TG(1-3)) tracts have been previously identified. In this study, we investigated telomere length in strains with two classes of mutations, one that resulted in short poly(TG(1-3)) tracts (tel1) and one that resulted in elongated tracts (pif1, rap1-17, rif1, or rif2). In the tel1 pif1 strain, Y' telomeres had about the same length as those in tel1 strains and X telomeres had lengths intermediate between those in tel1 and pif1 strains. Strains with either the tel1 rap1-17 or tel1 rif2 genotypes had short tracts for all chromosome ends examined, demonstrating that the telomere elongation characteristic of rap1-17 and rif2 strains is Tel1p-dependent. In strains of the tel1 rif1 or tel1 rif1 rif2 genotypes, telomeres with Y' repeats had short terminal tracts, whereas most of the X telomeres had long terminal tracts. These results demonstrate that the regulation of telomere length is different for X and Y' telomeres.

Authors
Craven, RJ; Petes, TD
MLA Citation
Craven, RJ, and Petes, TD. "Dependence of the regulation of telomere length on the type of subtelomeric repeat in the yeast Saccharomyces cerevisiae." Genetics 152.4 (August 1999): 1531-1541.
PMID
10430581
Source
pubmed
Published In
Genetics
Volume
152
Issue
4
Publish Date
1999
Start Page
1531
End Page
1541

Maximal stimulation of meiotic recombination by a yeast transcription factor requires the transcription activation domain and a DNA-binding domain.

The DNA sequences located upstream of the yeast HIS4 represent a very strong meiotic recombination hotspot. Although the activity of this hotspot requires the transcription activator Rap1p, the level of HIS4 transcription is not directly related to the level of recombination. We find that the recombination-stimulating activity of Rap1p requires the transcription activation domain of the protein. We show that a hybrid protein with the Gal4p DNA-binding domain and the Rap1p activation domain can stimulate recombination in a strain in which Gal4p-binding sites are inserted upstream of HIS4. In addition, we find recombination hotspot activity associated with the Gal4p DNA-binding sites that is independent of known transcription factors. We suggest that yeast cells have two types of recombination hotspots, alpha (transcription factor dependent) and beta (transcription factor independent).

Authors
Kirkpatrick, DT; Fan, Q; Petes, TD
MLA Citation
Kirkpatrick, DT, Fan, Q, and Petes, TD. "Maximal stimulation of meiotic recombination by a yeast transcription factor requires the transcription activation domain and a DNA-binding domain." Genetics 152.1 (May 1999): 101-115.
PMID
10224246
Source
pubmed
Published In
Genetics
Volume
152
Issue
1
Publish Date
1999
Start Page
101
End Page
115

Triplet repeats form secondary structures that escape DNA repair in yeast.

Several human neurodegenerative diseases result from expansion of CTG/CAG or CGG/CCG triplet repeats. The finding that single-stranded CNG repeats form hairpin-like structures in vitro has led to the hypothesis that DNA secondary structure formation is an important component of the expansion mechanism. We show that single-stranded DNA loops containing 10 CTG/CAG or CGG/CCG repeats are inefficiently repaired during meiotic recombination in Saccharomyces cerevisiae. Comparisons of the repair of DNA loops with palindromic and nonpalindromic sequences suggest that this inefficient repair reflects the ability of these sequences to form hairpin structures in vivo.

Authors
Moore, H; Greenwell, PW; Liu, CP; Arnheim, N; Petes, TD
MLA Citation
Moore, H, Greenwell, PW, Liu, CP, Arnheim, N, and Petes, TD. "Triplet repeats form secondary structures that escape DNA repair in yeast." Proc Natl Acad Sci U S A 96.4 (February 16, 1999): 1504-1509.
PMID
9990053
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
96
Issue
4
Publish Date
1999
Start Page
1504
End Page
1509

A mutation of the yeast gene encoding PCNA destabilizes both microsatellite and minisatellite DNA sequences.

The POL30 gene of the yeast Saccharomyces cerevisiae encodes the proliferating cell nuclear antigen (PCNA), a protein required for processive DNA synthesis by DNA polymerase delta and epsilon. We examined the effects of the pol30-52 mutation on the stability of microsatellite (1- to 8-bp repeat units) and minisatellite (20-bp repeat units) DNA sequences. It had previously been shown that this mutation destabilizes dinucleotide repeats 150-fold and that this effect is primarily due to defects in DNA mismatch repair. From our analysis of the effects of pol30-52 on classes of repetitive DNA with longer repeat unit lengths, we conclude that this mutation may also elevate the rate of DNA polymerase slippage. The effect of pol30-52 on tracts of repetitive DNA with large repeat unit lengths was similar, but not identical, to that observed previously for pol3-t, a temperature-sensitive mutation affecting DNA polymerase delta. Strains with both pol30-52 and pol3-t mutations grew extremely slowly and had minisatellite mutation rates considerably greater than those observed in either single mutant strain.

Authors
Kokoska, RJ; Stefanovic, L; Buermeyer, AB; Liskay, RM; Petes, TD
MLA Citation
Kokoska, RJ, Stefanovic, L, Buermeyer, AB, Liskay, RM, and Petes, TD. "A mutation of the yeast gene encoding PCNA destabilizes both microsatellite and minisatellite DNA sequences." Genetics 151.2 (February 1999): 511-519.
PMID
9927447
Source
pubmed
Published In
Genetics
Volume
151
Issue
2
Publish Date
1999
Start Page
511
End Page
519

Conversion-type and restoration-type repair of DNA mismatches formed during meiotic recombination in Saccharomyces cerevisiae.

Meiotic recombination in yeast is associated with heteroduplex formation. Heteroduplexes formed between nonidentical DNA strands contain DNA mismatches, and most DNA mismatches in wild-type strains are efficiently corrected. Although some patterns of mismatch correction result in non-Mendelian segregation of the heterozygous marker (gene conversion), one predicted pattern of correction (restoration-type repair) results in normal Mendelian segregation. Using a yeast strain in which a marker leading to a well-repaired mismatch is flanked by markers that lead to poorly repaired mismatches, we present direct evidence for restoration-type repair in yeast. In addition, we find that the frequency of tetrads with conversion-type repair is higher for a marker at the 5' end of the HIS4 gene than for a marker in the middle of the gene. These results suggest that the ratio of conversion-type to restoration-type repair may be important in generating gradients of gene conversion (polarity gradients).

Authors
Kirkpatrick, DT; Dominska, M; Petes, TD
MLA Citation
Kirkpatrick, DT, Dominska, M, and Petes, TD. "Conversion-type and restoration-type repair of DNA mismatches formed during meiotic recombination in Saccharomyces cerevisiae." Genetics 149.4 (August 1998): 1693-1705.
PMID
9691029
Source
pubmed
Published In
Genetics
Volume
149
Issue
4
Publish Date
1998
Start Page
1693
End Page
1705

Destabilization of yeast micro- and minisatellite DNA sequences by mutations affecting a nuclease involved in Okazaki fragment processing (rad27) and DNA polymerase delta (pol3-t).

We examined the effects of mutations in the Saccharomyces cerevisiae RAD27 (encoding a nuclease involved in the processing of Okazaki fragments) and POL3 (encoding DNA polymerase delta) genes on the stability of a minisatellite sequence (20-bp repeats) and microsatellites (1- to 8-bp repeat units). Both the rad27 and pol3-t mutations destabilized both classes of repeats, although the types of tract alterations observed in the two mutant strains were different. The tract alterations observed in rad27 strains were primarily additions, and those observed in pol3-t strains were primarily deletions. Measurements of the rates of repetitive tract alterations in strains with both rad27 and pol3-t indicated that the stimulation of microsatellite instability by rad27 was reduced by the effects of the pol3-t mutation. We also found that rad27 and pol3-01 (an allele carrying a mutation in the "proofreading" exonuclease domain of DNA polymerase delta) mutations were synthetically lethal.

Authors
Kokoska, RJ; Stefanovic, L; Tran, HT; Resnick, MA; Gordenin, DA; Petes, TD
MLA Citation
Kokoska, RJ, Stefanovic, L, Tran, HT, Resnick, MA, Gordenin, DA, and Petes, TD. "Destabilization of yeast micro- and minisatellite DNA sequences by mutations affecting a nuclease involved in Okazaki fragment processing (rad27) and DNA polymerase delta (pol3-t)." Mol Cell Biol 18.5 (May 1998): 2779-2788.
PMID
9566897
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
18
Issue
5
Publish Date
1998
Start Page
2779
End Page
2788

Genetic control of microsatellite instability in Saccharomyces cerevisiae

Authors
Sia, EA; Kokoska, RJ; Dominska, M; Greenwell, P; Petes, TD
MLA Citation
Sia, EA, Kokoska, RJ, Dominska, M, Greenwell, P, and Petes, TD. "Genetic control of microsatellite instability in Saccharomyces cerevisiae." 1998.
Source
wos-lite
Published In
STRUCTURE, MOTION, INTERACTION AND EXPRESSION OF BIOLOGICAL MACROMOLECULES, VOL 2
Publish Date
1998
Start Page
209
End Page
213

Microsatellite instability in yeast: dependence on the length of the microsatellite.

One of the most common microsatellites in eukaryotes consists of tandem arrays [usually 15-50 base pairs (bp) in length] of the dinucleotide GT. We examined the rates of instability for poly GT tracts of 15, 33, 51, 99 and 105 bp in wild-type and mismatch repair-deficient strains of Saccharomyces cerevisiae. Rates of instability increased more than two orders of magnitude as tracts increased in size from 15 to 99 bp in both wild-type and msh2 strains. The types of alterations observed in long and short tracts in wild-type strains were different in two ways. First, tracts > or = 51 bp had significantly more large deletions than tracts < or = 33 bp. Second, for the 99- and 105-bp tracts, almost all events involving single repeats were additions; for the smaller tracts, both additions and deletions of single repeats were common.

Authors
Wierdl, M; Dominska, M; Petes, TD
MLA Citation
Wierdl, M, Dominska, M, and Petes, TD. "Microsatellite instability in yeast: dependence on the length of the microsatellite." Genetics 146.3 (July 1997): 769-779.
PMID
9215886
Source
pubmed
Published In
Genetics
Volume
146
Issue
3
Publish Date
1997
Start Page
769
End Page
779

Repair of DNA loops involves DNA-mismatch and nucleotide-excision repair proteins.

A number of enzymes recognize and repair DNA lesions. The DNA-mismatch repair system corrects base-base mismatches and small loops, whereas the nucleotide-excision repair system removes pyrimidine dimers and other helix-distorting lesions. DNA molecules with mismatches or loops can arise as a consequence of heteroduplex formation during meiotic recombination. In the yeast Saccharomyces cerevisiae, repair of mismatches results in gene conversion or restoration, and failure to repair the mismatch results in post-meiotic segregation (PMS). The ratio of gene-conversion to PMS events reflects the efficiency of DNA repair. By examining the PMS patterns in yeast strains heterozygous for a mutant allele with a 26-base-pair insertion, we find that the repair of 26-base loops involves Msh2 (a DNA-mismatch repair protein) and Rad1 (a protein required for nucleotide-excision repair).

Authors
Kirkpatrick, DT; Petes, TD
MLA Citation
Kirkpatrick, DT, and Petes, TD. "Repair of DNA loops involves DNA-mismatch and nucleotide-excision repair proteins." Nature 387.6636 (June 26, 1997): 929-931.
PMID
9202128
Source
pubmed
Published In
Nature
Volume
387
Issue
6636
Publish Date
1997
Start Page
929
End Page
931
DOI
10.1038/43225

Stabilization of microsatellite sequences by variant repeats in the yeast Saccharomyces cerevisiae.

We examined the effect of a single variant repeat on the stability of a 51-base pair (bp) microsatellite (poly GT). We found that the insertion stabilizes the microsatellite about fivefold in wild-type strains. The stabilizing effect of the variant base was also observed in strains with mutations in the DNA mismatch repair genes pms1, msh2 and msh3, indicating that this effect does not require a functional DNA mismatch repair system. Most of the microsatellite alterations in the pms1, msh2 and msh3 strains were additions or deletions of single GT repeats, but about half of the alterations in the wild-type and msh6 strains were large (> 8 bp) deletions or additions.

Authors
Petes, TD; Greenwell, PW; Dominska, M
MLA Citation
Petes, TD, Greenwell, PW, and Dominska, M. "Stabilization of microsatellite sequences by variant repeats in the yeast Saccharomyces cerevisiae." Genetics 146.2 (June 1997): 491-498.
PMID
9178000
Source
pubmed
Published In
Genetics
Volume
146
Issue
2
Publish Date
1997
Start Page
491
End Page
498

Microsatellite instability in yeast: dependence on repeat unit size and DNA mismatch repair genes.

We examined the stability of microsatellites of different repeat unit lengths in Saccharomyces cerevisiae strains deficient in DNA mismatch repair. The msh2 and msh3 mutations destabilized microsatellites with repeat units of 1, 2, 4, 5, and 8 bp; a poly(G) tract of 18 bp was destabilized several thousand-fold by the msh2 mutation and about 100-fold by msh3. The msh6 mutations destabilized microsatellites with repeat units of 1 and 2 bp but had no effect on microsatellites with larger repeats. These results argue that coding sequences containing repetitive DNA tracts will be preferred target sites for mutations in human tumors with mismatch repair defects. We find that the DNA mismatch repair genes destabilize microsatellites with repeat units from 1 to 13 bp but have no effect on the stability of minisatellites with repeat units of 16 or 20 bp. Our data also suggest that displaced loops on the nascent strand, resulting from DNA polymerase slippage, are repaired differently than loops on the template strand.

Authors
Sia, EA; Kokoska, RJ; Dominska, M; Greenwell, P; Petes, TD
MLA Citation
Sia, EA, Kokoska, RJ, Dominska, M, Greenwell, P, and Petes, TD. "Microsatellite instability in yeast: dependence on repeat unit size and DNA mismatch repair genes." Mol Cell Biol 17.5 (May 1997): 2851-2858.
PMID
9111357
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
17
Issue
5
Publish Date
1997
Start Page
2851
End Page
2858

Competition between adjacent meiotic recombination hotspots in the yeast Saccharomyces cerevisiae.

In a wild-type strain of Saccharomyces cerevisiae, a hotspot for meiotic recombination is located upstream of the HIS4 gene. An insertion of a 49-bp telomeric sequence into the coding region of HIS4 strongly stimulates meiotic recombination and the local formation of meiosis-specific double-strand DNA breaks (DSBs). When strains are constructed in which both hotspots are heterozygous, hotspot activity is substantially less when the hotspots are on the same chromosome than when they are on opposite chromosomes.

Authors
Fan, QQ; Xu, F; White, MA; Petes, TD
MLA Citation
Fan, QQ, Xu, F, White, MA, and Petes, TD. "Competition between adjacent meiotic recombination hotspots in the yeast Saccharomyces cerevisiae." Genetics 145.3 (March 1997): 661-670.
PMID
9055076
Source
pubmed
Published In
Genetics
Volume
145
Issue
3
Publish Date
1997
Start Page
661
End Page
670

Genetic control of microsatellite stability.

Authors
Sia, EA; Jinks-Robertson, S; Petes, TD
MLA Citation
Sia, EA, Jinks-Robertson, S, and Petes, TD. "Genetic control of microsatellite stability." Mutat Res 383.1 (January 31, 1997): 61-70. (Review)
PMID
9042420
Source
pubmed
Published In
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume
383
Issue
1
Publish Date
1997
Start Page
61
End Page
70

Fine-structure mapping of meiosis-specific double-strand DNA breaks at a recombination hotspot associated with an insertion of telomeric sequences upstream of the HIS4 locus in yeast.

Meiotic recombination in Saccharomyces cerevisiae is initiated by double-strand DNA breaks (DSBs). Using two approaches, we mapped the position of DSBs associated with a recombination hotspot created by insertion of telomeric sequences into the region upstream of HIS4. We found that the breaks have no obvious sequence specificity and localize to a region of approximately 50 bp adjacent to the telomeric insertion. By mapping the breaks and by studies of the exonuclease III sensitivity of the broken ends, we conclude that most of the broken DNA molecules have blunt ends with 3'-hydroxyl groups.

Authors
Xu, F; Petes, TD
MLA Citation
Xu, F, and Petes, TD. "Fine-structure mapping of meiosis-specific double-strand DNA breaks at a recombination hotspot associated with an insertion of telomeric sequences upstream of the HIS4 locus in yeast." Genetics 143.3 (July 1996): 1115-1125.
PMID
8807286
Source
pubmed
Published In
Genetics
Volume
143
Issue
3
Publish Date
1996
Start Page
1115
End Page
1125

Destabilization of simple repetitive DNA sequences by transcription in yeast.

Simple repetitive DNA sequences in the eukaryotic genome frequently alter in length. In wild-type strains, we find that transcription through a repetitive poly GT tract destabilizes the tract four- to ninefold. In mismatch repair-deficient yeast strains, simple repeats are very unstable. High levels of transcription in such strains destabilize repetitive tracts an additional two- to threefold.

Authors
Wierdl, M; Greene, CN; Datta, A; Jinks-Robertson, S; Petes, TD
MLA Citation
Wierdl, M, Greene, CN, Datta, A, Jinks-Robertson, S, and Petes, TD. "Destabilization of simple repetitive DNA sequences by transcription in yeast." Genetics 143.2 (June 1996): 713-721.
PMID
8725221
Source
pubmed
Published In
Genetics
Volume
143
Issue
2
Publish Date
1996
Start Page
713
End Page
721

Relationship between nuclease-hypersensitive sites and meiotic recombination hot spot activity at the HIS4 locus of Saccharomyces cerevisiae.

Meiotic double-strand DNA breaks (DSBs), the lesions that initiate meiotic recombination at the HIS4 recombination hot spot, occur in a region upstream of the coding sequence associated with multiple DNase I-hypersensitive sites. Mutations in transcription factors that lead to loss of the DSBs result in the loss of some but not all DNase I-hypersensitive sites in the upstream region. A meiosis-specific change in chromatin structure is detected in strains with the wild-type hot spot but not in strains with alterations that elevate or reduce hot spot activity. The position and intensity of micrococcal nuclease-hypersensitive sites correlate poorly with the sites of DSB formation.

Authors
Fan, QQ; Petes, TD
MLA Citation
Fan, QQ, and Petes, TD. "Relationship between nuclease-hypersensitive sites and meiotic recombination hot spot activity at the HIS4 locus of Saccharomyces cerevisiae." Mol Cell Biol 16.5 (May 1996): 2037-2043.
PMID
8628269
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
16
Issue
5
Publish Date
1996
Start Page
2037
End Page
2043

The DNA-binding protein Hdf1p (a putative Ku homologue) is required for maintaining normal telomere length in Saccharomyces cerevisiae.

In mammalian cells, the Ku autoantigen is an end- binding DNA protein required for the repair of DNA breaks [Troelstra, C. and Jaspers, N.G.J. (1994) Curr. Biol., 4, 1149- 1151]. A yeast gene (HDF1) encoding a putative homologue of the 70 kDa subunit of Ku has recently been identified [Feldmann, H. and Winnacker, E. L. (1993) J. Biol. Chem., 268, 12895- 12900]. We find that hdf1 mutant strains have substantially shorter telomeres than wild-type strains. We speculate that Hdf1p may bind the natural ends of the chromosome, in addition to binding to the ends of broken DNA molecules. Strains with both an hdf1 mutation and a mutation in TEL 1 (a gene related to the human ataxia telangiectasia gene) have extremely short telomeres and grow slowly.

Authors
Porter, SE; Greenwell, PW; Ritchie, KB; Petes, TD
MLA Citation
Porter, SE, Greenwell, PW, Ritchie, KB, and Petes, TD. "The DNA-binding protein Hdf1p (a putative Ku homologue) is required for maintaining normal telomere length in Saccharomyces cerevisiae." Nucleic Acids Res 24.4 (February 15, 1996): 582-585.
PMID
8604297
Source
pubmed
Published In
Nucleic Acids Research
Volume
24
Issue
4
Publish Date
1996
Start Page
582
End Page
585

The stabilization of repetitive tracts of DNA by variant repeats requires a functional DNA mismatch repair system.

Simple repetitive tracts of DNA are unstable in all organisms thus far examined. In the yeast S. cerevisiae, we show that a 51 bp poly(GT) tract alters length at a rate of about 10(-5) per cell division. Insertion of a single variant repeat (either AT or CT) into the middle of the poly(GT) tract results in 100-fold stabilization. This stabilization requires the DNA mismatch repair system. Alterations within tracts with variant repeats occur more frequently on one side of the interruption than on the other. The stabilizing effects of variant repeats and polarity of repeat alterations have also been observed in trinucleotide repeats associated with certain human diseases.

Authors
Heale, SM; Petes, TD
MLA Citation
Heale, SM, and Petes, TD. "The stabilization of repetitive tracts of DNA by variant repeats requires a functional DNA mismatch repair system." Cell 83.4 (November 17, 1995): 539-545.
PMID
7585956
Source
pubmed
Published In
Cell
Volume
83
Issue
4
Publish Date
1995
Start Page
539
End Page
545

Mutations in the MSH3 gene preferentially lead to deletions within tracts of simple repetitive DNA in Saccharomyces cerevisiae.

Eukaryotic genomes contain tracts of DNA in which a single base or a small number of bases are repeated (microsatellites). Mutations in the yeast DNA mismatch repair genes MSH2, PMS1, and MLH1 increase the frequency of mutations for normal DNA sequences and destabilize microsatellites. Mutations of human homologs of MSH2, PMS1, and MLH1 also cause microsatellite instability and result in certain types of cancer. We find that a mutation in the yeast gene MSH3 that does not substantially affect the rate of spontaneous mutations at several loci increases microsatellite instability about 40-fold, preferentially causing deletions. We suggest that MSH3 has different substrate specificities than the other mismatch repair proteins and that the human MSH3 homolog (MRP1) may be mutated in some tumors with microsatellite instability.

Authors
Strand, M; Earley, MC; Crouse, GF; Petes, TD
MLA Citation
Strand, M, Earley, MC, Crouse, GF, and Petes, TD. "Mutations in the MSH3 gene preferentially lead to deletions within tracts of simple repetitive DNA in Saccharomyces cerevisiae." Proc Natl Acad Sci U S A 92.22 (October 24, 1995): 10418-10421.
PMID
7479796
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
92
Issue
22
Publish Date
1995
Start Page
10418
End Page
10421

TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene.

Yeast chromosomes terminate in tracts of simple repetitive DNA (poly[G1-3T]). Mutations in the gene TEL1 result in shortened telomeres. Sequence analysis of TEL1 indicates that it encodes a very large (322 kDa) protein with amino acid motifs found in phosphatidylinositol/protein kinases. The closest homolog to TEL1 is the human ataxia telangiectasia gene.

Authors
Greenwell, PW; Kronmal, SL; Porter, SE; Gassenhuber, J; Obermaier, B; Petes, TD
MLA Citation
Greenwell, PW, Kronmal, SL, Porter, SE, Gassenhuber, J, Obermaier, B, and Petes, TD. "TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene." Cell 82.5 (September 8, 1995): 823-829.
PMID
7671310
Source
pubmed
Published In
Cell
Volume
82
Issue
5
Publish Date
1995
Start Page
823
End Page
829

Meiosis-specific double-strand DNA breaks at the HIS4 recombination hot spot in the yeast Saccharomyces cerevisiae: control in cis and trans.

The region of Saccharomyces cerevisiae chromosome III located between the 5' end of the HIS4 gene and the 3' end of the adjacent BIK1 gene has a very high level of meiotic recombination. In wild-type strains, a meiosis-specific double-strand DNA break occurs in the hot spot region. This break is absent in strains in which the transcription factors Rap1p, Bas1p, and Bas2p cannot bind to the region upstream of HIS4. In strains with levels of recombination that are higher than those of the wild type, the break is found at elevated levels. The linear relationship between hot spot activity and the frequency of double-strand DNA breaks suggests that these lesions are responsible for initiating recombination at the HIS4 recombination hot spot.

Authors
Fan, Q; Xu, F; Petes, TD
MLA Citation
Fan, Q, Xu, F, and Petes, TD. "Meiosis-specific double-strand DNA breaks at the HIS4 recombination hot spot in the yeast Saccharomyces cerevisiae: control in cis and trans." Mol Cell Biol 15.3 (March 1995): 1679-1688.
PMID
7862159
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
15
Issue
3
Publish Date
1995
Start Page
1679
End Page
1688

2 Meiotic Sister Chromatid Recombination

Authors
Petes, TD; Pukkila, PJ
MLA Citation
Petes, TD, and Pukkila, PJ. "2 Meiotic Sister Chromatid Recombination." Advances in Genetics 33.C (1995): 41-62.
Source
scival
Published In
Advances in genetics
Volume
33
Issue
C
Publish Date
1995
Start Page
41
End Page
62
DOI
10.1016/S0065-2660(08)60330-2

Meiotic sister chromatid recombination.

Authors
Petes, TD; Pukkila, PJ
MLA Citation
Petes, TD, and Pukkila, PJ. "Meiotic sister chromatid recombination." Adv Genet 33 (1995): 41-62. (Review)
PMID
7484457
Source
pubmed
Published In
Advances in genetics
Volume
33
Publish Date
1995
Start Page
41
End Page
62

A novel structural form of the 2 micron plasmid of the yeast Saccharomyces cerevisiae.

DNA was isolated from cells of Saccharomyces cerevisiae incubated under conditions that enriched for DNA replication intermediates. A novel form of the 2 microns plasmid was detected, in which two monomeric or dimeric circles were joined by a linear double-stranded segment of variable length. We suggest that this molecule is a consequence of site-specific recombination within a dimeric DNA molecule during DNA replication. The existence of this molecule provides supporting physical evidence for a variant of the model of 2 mu plasmid amplification first proposed by Futcher (1986).

Authors
Petes, TD; Williamson, DH
MLA Citation
Petes, TD, and Williamson, DH. "A novel structural form of the 2 micron plasmid of the yeast Saccharomyces cerevisiae." Yeast 10.10 (October 1994): 1341-1345.
PMID
7900423
Source
pubmed
Published In
Yeast
Volume
10
Issue
10
Publish Date
1994
Start Page
1341
End Page
1345
DOI
10.1002/yea.320101011

Effect of mutations in genes affecting homologous recombination on restriction enzyme-mediated and illegitimate recombination in Saccharomyces cerevisiae.

Restriction enzyme-mediated events (REM events; integration of transforming DNA catalyzed by in vivo action of a restriction enzyme) and illegitimate recombination events (IR events; integration of transforming DNA that shares no homology with the host genomic sequences) have been previously characterized in Saccharomyces cerevisiae. This study determines the effect of mutations in genes that are involved in homologous recombination and/or in the repair of double-stranded DNA breaks on these recombination events. Surprisingly, REM events are completely independent of the double-strand-break repair functions encoded by the RAD51, RAD52, and RAD57 genes but require the RAD50 gene product. IR events are under different genetic control than homologous integration events. In the rad50 mutant, homologous integration occurred at wild-type frequency, whereas the frequency of IR events was 20- to 100-fold reduced. Conversely, the rad52 mutant was grossly deficient in homologous integration (at least 1,000-fold reduced) but showed only a 2- to 8-fold reduction in IR frequency.

Authors
Schiestl, RH; Zhu, J; Petes, TD
MLA Citation
Schiestl, RH, Zhu, J, and Petes, TD. "Effect of mutations in genes affecting homologous recombination on restriction enzyme-mediated and illegitimate recombination in Saccharomyces cerevisiae." Mol Cell Biol 14.7 (July 1994): 4493-4500.
PMID
8007955
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
14
Issue
7
Publish Date
1994
Start Page
4493
End Page
4500

Analysis of meiotic recombination events near a recombination hotspot in the yeast Saccharomyces cerevisiae.

The region of yeast chromosome III between the HIS4 and LEU2 genes has an unusually high frequency of meiotic recombination. In order to determine the pattern of cross-over and gene conversion events, we constructed a strain with a number of heterozygous markers in this 25-kb interval. We found that very high levels of recombination are localized to regions of DNA near HIS4. In addition, analysis of the patterns of co-conversion of adjacent markers suggests that there is more than one initiation site contributing to recombination of HIS4.

Authors
White, MA; Petes, TD
MLA Citation
White, MA, and Petes, TD. "Analysis of meiotic recombination events near a recombination hotspot in the yeast Saccharomyces cerevisiae." Curr Genet 26.1 (July 1994): 21-30.
PMID
7954892
Source
pubmed
Published In
Current Genetics
Volume
26
Issue
1
Publish Date
1994
Start Page
21
End Page
30

DESTABILIZATION OF TRACTS OF SIMPLE REPETITIVE DNA IN YEAST BY MUTATIONS AFFECTING DNA MISMATCH REPAIR (VOL 365, PG 274, 1993)

Authors
STRAND, M; PROLLA, TA; LISKAY, RM; PETES, TD
MLA Citation
STRAND, M, PROLLA, TA, LISKAY, RM, and PETES, TD. "DESTABILIZATION OF TRACTS OF SIMPLE REPETITIVE DNA IN YEAST BY MUTATIONS AFFECTING DNA MISMATCH REPAIR (VOL 365, PG 274, 1993)." NATURE 368.6471 (April 7, 1994): 569-569.
Source
wos-lite
Published In
Nature
Volume
368
Issue
6471
Publish Date
1994
Start Page
569
End Page
569

Polarity of meiotic gene conversion in fungi: contrasting views.

The frequency of meiotic gene conversion often varies linearly from one end of the gene to the other. This phenomenon has been called 'polarity'. In this review, we will primarily studies of polarity that have been done in the yeast Saccharomyces cerevisiae (ARG4 and HIS4 loci) and in Ascobolus (b2 locus) with an emphasis on possible mechanisms. The genetic and physical data obtained at these 'hotspots' of recombination strongly suggests that the formation of a polarity gradient reflects both the frequency of heteroduplex formation and the processing of this recombination intermediate by mismatch-repair-dependent processes.

Authors
Nicolas, A; Petes, TD
MLA Citation
Nicolas, A, and Petes, TD. "Polarity of meiotic gene conversion in fungi: contrasting views." Experientia 50.3 (March 15, 1994): 242-252. (Review)
PMID
8143798
Source
pubmed
Published In
Experientia
Volume
50
Issue
3
Publish Date
1994
Start Page
242
End Page
252

Instability of simple sequence repeats in a mammalian cell line.

Short tandem repeat sequences in the mammalian genome are considered to be unstable, since many of them are polymorphic in length; however, the extent of this instability has been difficult to quantitate. We have directly determined the rate of mutation of a simple sequence repeat in a mammalian cell line. A plasmid containing a dinucleotide repeat [poly(CA/GT)] that disrupts the reading frame of a downstream gene was integrated into the genome of a mouse cell line, and spontaneous revertants were selected. Reversion rates were more than 100 times higher in cells carrying the repeated sequence than in control cells that carried the same fusion gene with a 4-bp out-of-frame deletion. Revertant clones derived from the lines carrying the dinucleotide repeat had insertions or deletions of one or more repeat units.

Authors
Farber, RA; Petes, TD; Dominska, M; Hudgens, SS; Liskay, RM
MLA Citation
Farber, RA, Petes, TD, Dominska, M, Hudgens, SS, and Liskay, RM. "Instability of simple sequence repeats in a mammalian cell line." Hum Mol Genet 3.2 (February 1994): 253-256.
PMID
8004091
Source
pubmed
Published In
Human Molecular Genetics
Volume
3
Issue
2
Publish Date
1994
Start Page
253
End Page
256

Erratum: Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair (Nature 365, 274-276 (1993))

Authors
Strand, M; Prolla, TA; Liskay, RM; Petes, TD
MLA Citation
Strand, M, Prolla, TA, Liskay, RM, and Petes, TD. "Erratum: Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair (Nature 365, 274-276 (1993))." Nature 368.6471 (1994): 569--.
Source
scival
Published In
Nature
Volume
368
Issue
6471
Publish Date
1994
Start Page
569-
DOI
10.1038/368569a0

Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair.

The genomes of all eukaryotes contain tracts of DNA in which a single base or a small number of bases is repeated. Expansions of such tracts have been associated with several human disorders including the fragile X syndrome. In addition, simple repeats are unstable in certain forms of colorectal cancer, suggesting a defect in DNA replication or repair. We show here that mutations in any three yeast genes involved in DNA mismatch repair (PMS1, MLH1 and MSH2) lead to 100- to 700-fold increases in tract instability, whereas mutations that eliminate the proof-reading function of DNA polymerases have little effect. The meiotic stability of the tracts is similar to the mitotic stability. These results suggest that tract instability is associated with DNA polymerases slipping during replication, and that some types of colorectal cancer may reflect mutations in genes involved in DNA mismatch repair.

Authors
Strand, M; Prolla, TA; Liskay, RM; Petes, TD
MLA Citation
Strand, M, Prolla, TA, Liskay, RM, and Petes, TD. "Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair." Nature 365.6443 (September 16, 1993): 274-276.
PMID
8371783
Source
pubmed
Published In
Nature
Volume
365
Issue
6443
Publish Date
1993
Start Page
274
End Page
276
DOI
10.1038/365274a0

INSTABILITY OF MICROSATELLITE SEQUENCES IN CULTURED-CELLS

Authors
FARBER, RA; PETES, TD; DOMINSKA, M; HUDGENS, SS; LISKAY, RM
MLA Citation
FARBER, RA, PETES, TD, DOMINSKA, M, HUDGENS, SS, and LISKAY, RM. "INSTABILITY OF MICROSATELLITE SEQUENCES IN CULTURED-CELLS." AMERICAN JOURNAL OF HUMAN GENETICS 53.3 (September 1993): 21-21.
Source
wos-lite
Published In
The American Journal of Human Genetics
Volume
53
Issue
3
Publish Date
1993
Start Page
21
End Page
21

Transcription factors are required for the meiotic recombination hotspot at the HIS4 locus in Saccharomyces cerevisiae.

The full activity of a recombination initiation site located 5' of HIS4 requires the binding of the transcription factors RAP1, BAS1, and BAS2. Two RAP1 binding sites can substitute for the wild-type initiation site. A 51-bp region of telomeric DNA inserted upstream of either HIS4 or ARG4 very strongly stimulates recombination. We suggest that the ability of transcription factors to induce recombination is a consequence of an altered chromatin structure that favors the entry of proteins that initiate recombination, rather than an effect of these factors on transcription.

Authors
White, MA; Dominska, M; Petes, TD
MLA Citation
White, MA, Dominska, M, and Petes, TD. "Transcription factors are required for the meiotic recombination hotspot at the HIS4 locus in Saccharomyces cerevisiae." Proc Natl Acad Sci U S A 90.14 (July 15, 1993): 6621-6625.
PMID
8341678
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
90
Issue
14
Publish Date
1993
Start Page
6621
End Page
6625

Instability of a plasmid-borne inverted repeat in Saccharomyces cerevisiae.

Inverted repeated DNA sequences are common in both prokaryotes and eukaryotes. We found that a plasmid-borne 94 base-pair inverted repeat (a perfect palindrome of 47 bp) containing a poly GT sequence is unstable in S. cerevisiae, with a minimal deletion frequency of about 10(-4)/mitotic division. Ten independent deletions had identical end points. Sequence analysis indicated that all deletions were the result of a DNA polymerase slippage event (or a recombination event) involving a 5-bp repeat (5' CGACG 3') that flanked the inverted repeat. The deletion rate and the types of deletions were unaffected by the rad52 mutation. Strains with the pms1 mutation had a 10-fold elevated frequency of instability of the inverted repeat. The types of sequence alterations observed in the pms1 background, however, were different than those seen in either the wild-type or rad52 genetic backgrounds.

Authors
Henderson, ST; Petes, TD
MLA Citation
Henderson, ST, and Petes, TD. "Instability of a plasmid-borne inverted repeat in Saccharomyces cerevisiae." Genetics 134.1 (May 1993): 57-62.
PMID
8514149
Source
pubmed
Published In
Genetics
Volume
134
Issue
1
Publish Date
1993
Start Page
57
End Page
62

Genetic evidence that the meiotic recombination hotspot at the HIS4 locus of Saccharomyces cerevisiae does not represent a site for a symmetrically processed double-strand break.

In the yeast Saccharomyces cerevisiae, the binding of the Rap1 protein to a site located between the 5' end of the HIS4 gene and the 3' end of BIK1 stimulates meiotic recombination at both flanking loci. By using strains that contain mutations located in HIS4 and BIK1, we found that most recombination events stimulated by the binding of Rap1 involve HIS4 or BIK1, rather than bidirectional events including both loci. The patterns of aberrant segregation indicate that most of the Rap1-stimulated recombination events do not represent the symmetric processing of a double-strand DNA break located at the Rap1-binding site.

Authors
Porter, SE; White, MA; Petes, TD
MLA Citation
Porter, SE, White, MA, and Petes, TD. "Genetic evidence that the meiotic recombination hotspot at the HIS4 locus of Saccharomyces cerevisiae does not represent a site for a symmetrically processed double-strand break." Genetics 134.1 (May 1993): 5-19.
PMID
8514148
Source
pubmed
Published In
Genetics
Volume
134
Issue
1
Publish Date
1993
Start Page
5
End Page
19

Transformation of Saccharomyces cerevisiae with nonhomologous DNA: illegitimate integration of transforming DNA into yeast chromosomes and in vivo ligation of transforming DNA to mitochondrial DNA sequences.

When the yeast Saccharomyces cerevisiae was transformed with DNA that shares no homology to the genome, three classes of transformants were obtained. In the most common class, the DNA was inserted as the result of a reaction that appears to require base pairing between the target sequence and the terminal few base pairs of the transforming DNA fragment. In the second class, no such homology was detected, and the transforming DNA was integrated next to a CTT or GTT in the target; it is likely that these integration events were mediated by topoisomerase I. The final class involved the in vivo ligation of transforming DNA with nucleus-localized linear fragments of mitochondrial DNA.

Authors
Schiestl, RH; Dominska, M; Petes, TD
MLA Citation
Schiestl, RH, Dominska, M, and Petes, TD. "Transformation of Saccharomyces cerevisiae with nonhomologous DNA: illegitimate integration of transforming DNA into yeast chromosomes and in vivo ligation of transforming DNA to mitochondrial DNA sequences." Mol Cell Biol 13.5 (May 1993): 2697-2705.
PMID
8386316
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
13
Issue
5
Publish Date
1993
Start Page
2697
End Page
2705

Physical detection of heteroduplexes during meiotic recombination in the yeast Saccharomyces cerevisiae.

We describe a general physical method for detecting the heteroduplex DNA that is formed as an intermediate in meiotic recombination in the yeast Saccharomyces cerevisiae. We use this method to study the kinetic relationship between the formation of heteroduplex DNA and other meiotic events. We show that strains with the rad50, but not the rad52, mutation are defective in heteroduplex formation. We also demonstrate that, although cruciform structures can be formed in vivo as a consequence of heteroduplex formation between DNA strands that contain different palindromic insertions, small palindromic sequences in homoduplex DNA are rarely extruded into the cruciform conformation.

Authors
Nag, DK; Petes, TD
MLA Citation
Nag, DK, and Petes, TD. "Physical detection of heteroduplexes during meiotic recombination in the yeast Saccharomyces cerevisiae." Mol Cell Biol 13.4 (April 1993): 2324-2331.
PMID
8455614
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
13
Issue
4
Publish Date
1993
Start Page
2324
End Page
2331

Experimental determination of rates of concerted evolution.

Authors
Jinks-Robertson, S; Petes, TD
MLA Citation
Jinks-Robertson, S, and Petes, TD. "Experimental determination of rates of concerted evolution." Methods Enzymol 224 (1993): 631-646.
PMID
8264416
Source
pubmed
Published In
Methods in Enzymology
Volume
224
Publish Date
1993
Start Page
631
End Page
646

GENETIC-CONTROL OF SIMPLE SEQUENCE STABILITY IN YEAST

Authors
LUSTIG, AJ; PETES, TD
MLA Citation
LUSTIG, AJ, and PETES, TD. "GENETIC-CONTROL OF SIMPLE SEQUENCE STABILITY IN YEAST." 1993.
Source
wos-lite
Volume
7
Publish Date
1993
Start Page
79
End Page
106

Analysis of a gene conversion gradient at the HIS4 locus in Saccharomyces cerevisiae.

Heteroduplexes formed between genes on homologous chromosomes are intermediates in meiotic recombination. In the HIS4 gene of Saccharomyces cerevisiae, most mutant alleles at the 5' end of the gene have a higher rate of meiotic recombination (gene conversion) than mutant alleles at the 3' end of the gene. Such gradients are usually interpreted as indicating a higher frequency of heteroduplex formation at the high conversion end of the gene. We present evidence indicating that the gradient of conversion at HIS4 primarily reflects the direction of mismatch repair rather than the frequency of heteroduplex formation. We also identify a site located between the 5' end of HIS4 and the 3' end of BIK1 that stimulates heteroduplex formation at HIS4 and BIK1.

Authors
Detloff, P; White, MA; Petes, TD
MLA Citation
Detloff, P, White, MA, and Petes, TD. "Analysis of a gene conversion gradient at the HIS4 locus in Saccharomyces cerevisiae." Genetics 132.1 (September 1992): 113-123.
PMID
1398048
Source
pubmed
Published In
Genetics
Volume
132
Issue
1
Publish Date
1992
Start Page
113
End Page
123

Saccharomyces cerevisiae RAD5-encoded DNA repair protein contains DNA helicase and zinc-binding sequence motifs and affects the stability of simple repetitive sequences in the genome.

rad5 (rev2) mutants of Saccharomyces cerevisiae are sensitive to UV light and other DNA-damaging agents, and RAD5 is in the RAD6 epistasis group of DNA repair genes. To unambiguously define the function of RAD5, we have cloned the RAD5 gene, determined the effects of the rad5 deletion mutation on DNA repair, DNA damage-induced mutagenesis, and other cellular processes, and analyzed the sequence of RAD5-encoded protein. Our genetic studies indicate that RAD5 functions primarily with RAD18 in error-free postreplication repair. We also show that RAD5 affects the rate of instability of poly(GT) repeat sequences. Genomic poly(GT) sequences normally change length at a rate of about 10(-4); this rate is approximately 10-fold lower in the rad5 deletion mutant than in the corresponding isogenic wild-type strain. RAD5 encodes a protein of 1,169 amino acids of M(r) 134,000, and it contains several interesting sequence motifs. All seven conserved domains found associated with DNA helicases are present in RAD5. RAD5 also contains a cysteine-rich sequence motif that resembles the corresponding sequences found in 11 other proteins, including those encoded by the DNA repair gene RAD18 and the RAG1 gene required for immunoglobin gene arrangement. A leucine zipper motif preceded by a basic region is also present in RAD5. The cysteine-rich region may coordinate the binding of zinc; this region and the basic segment might constitute distinct DNA-binding domains in RAD5. Possible roles of RAD5 putative ATPase/DNA helicase activity in DNA repair and in the maintenance of wild-type rates of instability of simple repetitive sequences are discussed.

Authors
Johnson, RE; Henderson, ST; Petes, TD; Prakash, S; Bankmann, M; Prakash, L
MLA Citation
Johnson, RE, Henderson, ST, Petes, TD, Prakash, S, Bankmann, M, and Prakash, L. "Saccharomyces cerevisiae RAD5-encoded DNA repair protein contains DNA helicase and zinc-binding sequence motifs and affects the stability of simple repetitive sequences in the genome." Mol Cell Biol 12.9 (September 1992): 3807-3818.
PMID
1324406
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
12
Issue
9
Publish Date
1992
Start Page
3807
End Page
3818

Instability of simple sequence DNA in Saccharomyces cerevisiae.

All eukaryotic genomes thus far examined contain simple sequence repeats. A particularly common simple sequence in many organisms (including humans) consists of tracts of alternating GT residues on one strand. Allelic poly(GT) tracts are often of different lengths in different individuals, indicating that they are likely to be unstable. We examined the instability of poly(GT) and poly(G) tracts in the yeast Saccharomyces cerevisiae. We found that these tracts were dramatically unstable, altering length at a minimal rate of 10(-4) events per division. Most of the changes involved one or two repeat unit additions or deletions, although one alteration involved an interaction with the yeast telomeres.

Authors
Henderson, ST; Petes, TD
MLA Citation
Henderson, ST, and Petes, TD. "Instability of simple sequence DNA in Saccharomyces cerevisiae." Mol Cell Biol 12.6 (June 1992): 2749-2757.
PMID
1588966
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
12
Issue
6
Publish Date
1992
Start Page
2749
End Page
2757

Measurements of excision repair tracts formed during meiotic recombination in Saccharomyces cerevisiae.

During meiotic recombination in the yeast Saccharomyces cerevisiae, heteroduplexes are formed at a high frequency between HIS4 genes located on homologous chromosomes. Using mutant alleles of the HIS4 gene that result in poorly repaired mismatches in heteroduplex DNA, we find that heteroduplexes often span a distance of 1.8 kb. In addition, we show that about one-third of the repair tracts initiated at well-repaired mismatches extend 900 bp.

Authors
Detloff, P; Petes, TD
MLA Citation
Detloff, P, and Petes, TD. "Measurements of excision repair tracts formed during meiotic recombination in Saccharomyces cerevisiae." Mol Cell Biol 12.4 (April 1992): 1805-1814.
PMID
1549127
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
12
Issue
4
Publish Date
1992
Start Page
1805
End Page
1814

A promoter deletion reduces the rate of mitotic, but not meiotic, recombination at the HIS4 locus in yeast.

Several investigators have reported that transcription stimulates some types of mitotic recombination in the yeast Saccharomyces cerevisiae. We find that mutations that reduce the rate of transcription of the yeast HIS4 gene in vegetative cells reduce the frequency of mitotic, but not meiotic, recombination events.

Authors
White, MA; Detloff, P; Strand, M; Petes, TD
MLA Citation
White, MA, Detloff, P, Strand, M, and Petes, TD. "A promoter deletion reduces the rate of mitotic, but not meiotic, recombination at the HIS4 locus in yeast." Curr Genet 21.2 (February 1992): 109-116.
PMID
1568254
Source
pubmed
Published In
Current Genetics
Volume
21
Issue
2
Publish Date
1992
Start Page
109
End Page
116

DNA-binding protein RAP1 stimulates meiotic recombination at the HIS4 locus in yeast.

In the yeast Saccharomyces cerevisiae, as in other eukaryotes, some regions of the genome have a much higher rate of meiotic recombination than others. We show below that the binding of the RAP1 protein to a site upstream of the HIS4 gene is necessary for a high rate of meiotic (but not mitotic) recombination at this locus. A mutation in the RAP1 binding site at HIS4 results in a decrease in recombination; overproduction of RAP1 causes an increase in recombination at HIS4 above wild-type levels.

Authors
White, MA; Wierdl, M; Detloff, P; Petes, TD
MLA Citation
White, MA, Wierdl, M, Detloff, P, and Petes, TD. "DNA-binding protein RAP1 stimulates meiotic recombination at the HIS4 locus in yeast." Proc Natl Acad Sci U S A 88.21 (November 1, 1991): 9755-9759.
PMID
1946399
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
88
Issue
21
Publish Date
1991
Start Page
9755
End Page
9759

Seven-base-pair inverted repeats in DNA form stable hairpins in vivo in Saccharomyces cerevisiae.

Palindromic sequences in single-stranded DNA and RNA have the potential for intrastrand base pairing, resulting in formation of "hairpin" structures. We previously reported a genetic method for detecting such structures in vivo in the yeast Saccharomyces cerevisiae. Below, we describe evidence indicating that a 14-base-pair palindrome (7 bp per inverted repeat) is sufficient for formation of a hairpin in vivo.

Authors
Nag, DK; Petes, TD
MLA Citation
Nag, DK, and Petes, TD. "Seven-base-pair inverted repeats in DNA form stable hairpins in vivo in Saccharomyces cerevisiae." Genetics 129.3 (November 1991): 669-673.
PMID
1752412
Source
pubmed
Published In
Genetics
Volume
129
Issue
3
Publish Date
1991
Start Page
669
End Page
673

7-BASE-PAIR INVERTED REPEATS IN DNA FORM STABLE HAIRPINS INVIVO IN SACCHAROMYCES-CEREVISIAE

Authors
NAG, DK; PETES, TD
MLA Citation
NAG, DK, and PETES, TD. "7-BASE-PAIR INVERTED REPEATS IN DNA FORM STABLE HAIRPINS INVIVO IN SACCHAROMYCES-CEREVISIAE." GENETICS 129.3 (November 1991): 669-673.
Source
wos-lite
Published In
Genetics
Volume
129
Issue
3
Publish Date
1991
Start Page
669
End Page
673

Integration of DNA fragments by illegitimate recombination in Saccharomyces cerevisiae.

DNA fragments (generated by BamHI treatment) with no homology to the yeast genome were transformed into Saccharomyces cerevisiae. When the fragments were transformed in the presence of the BamHI enzyme, they integrated into genomic BamHI sites. When the fragments were transformed in the absence of the enzyme, they integrated into genomic G-A-T-C sites. Since the G-A-T-C sequence is present at the ends of BamHI fragments, this results indicates that four base pairs of homology are sufficient for some types of mitotic recombination.

Authors
Schiestl, RH; Petes, TD
MLA Citation
Schiestl, RH, and Petes, TD. "Integration of DNA fragments by illegitimate recombination in Saccharomyces cerevisiae." Proc Natl Acad Sci U S A 88.17 (September 1, 1991): 7585-7589.
PMID
1881899
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
88
Issue
17
Publish Date
1991
Start Page
7585
End Page
7589

Genetic analysis of a meiotic recombination hotspot on chromosome III of Saccharomyces cerevisiae.

In a previous study, we analyzed meiotic recombination events that occurred in the 22-kb region (LEU2 to CEN3) of chromosome III of Saccharomyces cerevisiae. We found one region with an enhanced level of crossovers (a hotspot) and one region with a depressed level of crossovers. In this study, we show that about one-third of the crossovers that occur between LEU2 and CEN3 are initiated in a 1.3-kb region located approximately 6 kb from the centromere. Both crossovers and gene conversion events are initiated at this site. Events initiated at this position can be resolved as crossovers in regions located either centromere-distally or centromere-proximally from the initiation site.

Authors
Symington, LS; Brown, A; Oliver, SG; Greenwell, P; Petes, TD
MLA Citation
Symington, LS, Brown, A, Oliver, SG, Greenwell, P, and Petes, TD. "Genetic analysis of a meiotic recombination hotspot on chromosome III of Saccharomyces cerevisiae." Genetics 128.4 (August 1991): 717-727.
PMID
1840557
Source
pubmed
Published In
Genetics
Volume
128
Issue
4
Publish Date
1991
Start Page
717
End Page
727

Repair of specific base pair mismatches formed during meiotic recombination in the yeast Saccharomyces cerevisiae.

Heteroduplexes formed between DNA strands derived from different homologous chromosomes are an intermediate in meiotic crossing over in the yeast Saccharomyces cerevisiae and other eucaryotes. A heteroduplex formed between wild-type and mutant genes will contain a base pair mismatch; failure to repair this mismatch will lead to postmeiotic segregation (PMS). By analyzing the frequency of PMS for various mutant alleles in the yeast HIS4 gene, we showed that C/C mismatches were inefficiently repaired relative to all other point mismatches. These other mismatches (G/G, G/A, T/T, A/A, T/C, C/A, A/A, and T/G) were repaired with approximately the same efficiency. We found that in spores with unrepaired mismatches in heteroduplexes, the nontranscribed strand of the HIS4 gene was more frequently donated than the transcribed strand. In addition, the direction of repair for certain mismatches was nonrandom.

Authors
Detloff, P; Sieber, J; Petes, TD
MLA Citation
Detloff, P, Sieber, J, and Petes, TD. "Repair of specific base pair mismatches formed during meiotic recombination in the yeast Saccharomyces cerevisiae." Mol Cell Biol 11.2 (February 1991): 737-745.
PMID
1990280
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
11
Issue
2
Publish Date
1991
Start Page
737
End Page
745

The Tn3 beta-lactamase gene acts as a hotspot for meiotic recombination in yeast.

Although genetic distances are often assumed to be proportional to physical distances, chromosomal regions with unusually high (hotspots) or low (coldspots) levels of meiotic recombination have been described in a number of genetic systems. In general, the DNA sequences responsible for these effects have not been determined. We report that the 5' region of the beta-lactamase (ampR) gene of the bacterial transposon Tn3 is a hotspot for meiotic recombination when inserted into the chromosomes of the yeast Saccharomyces cerevisiae. When these sequences are homozygous, both crossing over and gene conversion are locally stimulated. The 5' end of the beta-lactamase gene is about 100-fold "hotter" for crossovers than an average yeast DNA sequence.

Authors
Stapleton, A; Petes, TD
MLA Citation
Stapleton, A, and Petes, TD. "The Tn3 beta-lactamase gene acts as a hotspot for meiotic recombination in yeast." Genetics 127.1 (January 1991): 39-51.
PMID
1849855
Source
pubmed
Published In
Genetics
Volume
127
Issue
1
Publish Date
1991
Start Page
39
End Page
51

The Tn3 β-lactamase gene acts as a hotspot for meiotic recombination in yeast

Although genetic distances are often assumed to be proportional to physical distances, chromosomal regions with unusually high (hotspots) or low (coldspots) levels of meiotic recombination have been described in a number of genetic systems. In general, the DNA sequences responsible for these effects have not been determined. We report that the 5' region of the β-lactamase (amp(R)) gene of the bacterial transposon Tn3 is a hotspot for meiotic recombination when inserted into the chromosomes of the yeast Saccharomyces cerevisiae. When these sequences are homozygous, both crossing over and gene conversion are locally stimulated. The 5' end of the β-lactamase gene is about 100-fold 'hotter' for crossovers than an average yeast DNA sequence.

Authors
Stapleton, A; Petes, TD
MLA Citation
Stapleton, A, and Petes, TD. "The Tn3 β-lactamase gene acts as a hotspot for meiotic recombination in yeast." Genetics 127.1 (1991): 39-51.
Source
scival
Published In
Genetics
Volume
127
Issue
1
Publish Date
1991
Start Page
39
End Page
51

Meiotic recombination between dispersed repeated genes is associated with heteroduplex formation.

In Saccharomyces cerevisiae, recombination events occurring between allelic genes located on homologous chromosomes are often associated with heteroduplex formation. We found that recombination events between repeated genes on nonhomologous chromosomes (ectopic events) are also associated with the formation of heteroduplexes, indicating that classical and ectopic recombination events involve similar mechanisms.

Authors
Nag, DK; Petes, TD
MLA Citation
Nag, DK, and Petes, TD. "Meiotic recombination between dispersed repeated genes is associated with heteroduplex formation." Mol Cell Biol 10.8 (August 1990): 4420-4423.
PMID
2196454
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
10
Issue
8
Publish Date
1990
Start Page
4420
End Page
4423

Genetic evidence for preferential strand transfer during meiotic recombination in yeast.

During meiotic recombination in the yeast Saccharomyces cerevisiae, heteroduplexes are formed as an intermediate in the exchange process. In the formation of an asymmetric heteroduplex, one chromosome acts as a donor of a single DNA strand and the other acts as a recipient. We present genetic evidence that the nontranscribed strand is donated more frequently than the transcribed strand in spores that have an unrepaired mismatch at the HIS4 locus.

Authors
Nag, DK; Petes, TD
MLA Citation
Nag, DK, and Petes, TD. "Genetic evidence for preferential strand transfer during meiotic recombination in yeast." Genetics 125.4 (August 1990): 753-761.
PMID
2204581
Source
pubmed
Published In
Genetics
Volume
125
Issue
4
Publish Date
1990
Start Page
753
End Page
761

Mitotic and meiotic gene conversion of Ty elements and other insertions in Saccharomyces cerevisiae.

We examined meiotic and mitotic gene conversion events involved in deletion of Ty elements and other insertions from the genome of the yeast Saccharomyces cerevisiae. We found that Ty elements and one other insertion were deleted by mitotic gene conversion less frequently than point mutations at the same loci. One non-Ty insertion similar in size to Ty, however, did not show this bias. Mitotic conversion events deleting insertions were more frequently associated with crossing over than those deleting point mutations. In meiosis, conversion events duplicating the element were more common than those that deleted the element for one of the loci (HIS4) examined.

Authors
Vincent, A; Petes, TD
MLA Citation
Vincent, A, and Petes, TD. "Mitotic and meiotic gene conversion of Ty elements and other insertions in Saccharomyces cerevisiae." Genetics 122.4 (August 1989): 759-772.
PMID
2547693
Source
pubmed
Published In
Genetics
Volume
122
Issue
4
Publish Date
1989
Start Page
759
End Page
772

Palindromic sequences in heteroduplex DNA inhibit mismatch repair in yeast.

Although single heterozygous markers in yeast usually segregate during meiosis in a 2:2 ratio, abberant 3:1 segregations occur quite frequently as a result of gene-conversion events. A second type of aberrant segregation, post-meiotic segregation, results from the segregation of two genotypes from a single haploid spore; in yeast such events are detected as sectored spore colonies and usually occur rarely. Post-meiotic segregation is thought to result from the replication of heteroduplex DNA formed during meiotic recombination. We report here that if the heteroduplex includes a palindromic insertion sequence, a high frequency of post-meiotic segregation results. This suggests that palindromic insertions are poorly repaired, which may be the result of hairpin-loop formation that affects the efficiency of repair of heteroduplex DNA.

Authors
Nag, DK; White, MA; Petes, TD
MLA Citation
Nag, DK, White, MA, and Petes, TD. "Palindromic sequences in heteroduplex DNA inhibit mismatch repair in yeast." Nature 340.6231 (July 27, 1989): 318-320.
PMID
2546083
Source
pubmed
Published In
Nature
Volume
340
Issue
6231
Publish Date
1989
Start Page
318
End Page
320
DOI
10.1038/340318a0

Recombination in yeast and the recombinant DNA technology.

The development of methods to isolate eukaryotic genes, alter these genes in vitro and reintroduce them into the cell has had a major impact on the study of recombination in the yeast Saccharomyces cerevisiae. In this paper we discuss how recombinant DNA techniques have been employed in the study of recombination in yeast and the results that have been obtained in these studies.

Authors
Petes, TD; Detloff, P; Jinks-Robertson, S; Judd, SR; Kupiec, M; Nag, D; Stapleton, A; Symington, LS; Vincent, A; White, M
MLA Citation
Petes, TD, Detloff, P, Jinks-Robertson, S, Judd, SR, Kupiec, M, Nag, D, Stapleton, A, Symington, LS, Vincent, A, and White, M. "Recombination in yeast and the recombinant DNA technology." Genome 31.2 (1989): 536-540. (Review)
PMID
2698829
Source
pubmed
Published In
Genome / National Research Council Canada = Genome / Conseil national de recherches Canada
Volume
31
Issue
2
Publish Date
1989
Start Page
536
End Page
540

Mitotic recombination within the centromere of a yeast chromosome.

Centromeres are the structural elements of eukaryotic chromosomes that hold sister chromatids together and to which spindle tubules connect during cell division. Centromeres have been shown to suppress meiotic recombination in some systems. In this study yeast strains genetically marked within and flanking a centromere, were used to demonstrate that gene conversion (nonreciprocal recombination) tracts in mitosis can enter into and extend through the centromere.

Authors
Liebman, SW; Symington, LS; Petes, TD
MLA Citation
Liebman, SW, Symington, LS, and Petes, TD. "Mitotic recombination within the centromere of a yeast chromosome." Science 241.4869 (August 26, 1988): 1074-1077.
PMID
3137657
Source
pubmed
Published In
Science
Volume
241
Issue
4869
Publish Date
1988
Start Page
1074
End Page
1077

Meiotic recombination between repeated transposable elements in Saccharomyces cerevisiae.

We have measured the frequency of meiotic recombination between marked Ty elements in the Saccharomyces cerevisiae genome. These recombination events were usually nonreciprocal (gene conversions) and sometimes involved nonhomologous chromosomes. The frequency of ectopic gene conversion among Ty elements appeared lower than expected on the basis of previous studies of recombination between artificially constructed repeats. The conversion events involved either a subset of the total Ty elements in the genome or the conversion tract was restricted to a small region of the Ty element. In addition, the observed conversion events were very infrequently associated with reciprocal exchange.

Authors
Kupiec, M; Petes, TD
MLA Citation
Kupiec, M, and Petes, TD. "Meiotic recombination between repeated transposable elements in Saccharomyces cerevisiae." Mol Cell Biol 8.7 (July 1988): 2942-2954.
PMID
2841590
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
8
Issue
7
Publish Date
1988
Start Page
2942
End Page
2954

Allelic and ectopic recombination between Ty elements in yeast.

Allelic and nonallelic (ectopic) recombination events were analyzed in a set of isogenic strains that carry marked Ty elements. We found that allelic recombination between Ty elements occurred at normal frequencies both in meiosis and mitosis. The marked Ty elements were involved in a large variety of different types of ectopic recombination and this variety was greater in mitosis than in meiosis. Allelic and ectopic recombination events occurred at similar frequencies in mitosis, but allelic recombination predominated in meiosis. Some of the types of ectopic mitotic recombination indicated the common occurrence of concerted recombination events. The length of homology represented by a delta element (330 bp) seemed to be sufficient for some types of mitotic and meiotic recombination.

Authors
Kupiec, M; Petes, TD
MLA Citation
Kupiec, M, and Petes, TD. "Allelic and ectopic recombination between Ty elements in yeast." Genetics 119.3 (July 1988): 549-559.
PMID
2841187
Source
pubmed
Published In
Genetics
Volume
119
Issue
3
Publish Date
1988
Start Page
549
End Page
559

Physical lengths of meiotic and mitotic gene conversion tracts in Saccharomyces cerevisiae.

Physical lengths of gene conversion tracts for meiotic and mitotic conversions were examined, using the same diploid yeast strain in all experiments. This strain is heterozygous for a mutation in the URA3 gene as well as closely linked restriction site markers. In cells that had a gene conversion event at the URA3 locus, it was determined by Southern analysis which of the flanking heterozygous restriction sites had co-converted. It was found that mitotic conversion tracts were longer on the average than meiotic tracts. About half of the tracts generated by spontaneous mitotic gene conversion included heterozygous markers 4.2 kb apart; none of the meiotic conversions included these markers. Stimulation of mitotic gene conversion by ultraviolet light or methylmethanesulfonate had no obvious effect on the size or distribution of the tracts. Almost all conversion tracts were continuous.

Authors
Judd, SR; Petes, TD
MLA Citation
Judd, SR, and Petes, TD. "Physical lengths of meiotic and mitotic gene conversion tracts in Saccharomyces cerevisiae." Genetics 118.3 (March 1988): 401-410.
PMID
2835285
Source
pubmed
Published In
Genetics
Volume
118
Issue
3
Publish Date
1988
Start Page
401
End Page
410

Expansions and contractions of the genetic map relative to the physical map of yeast chromosome III.

To examine the relationship between genetic and physical chromosome maps, we constructed a diploid strain of the yeast Saccharomyces cerevisiae heterozygous for 12 restriction site mutations within a 23-kilobase (5-centimorgan) interval of chromosome III. Crossovers were not uniformly distributed along the chromosome, one interval containing significantly more and one interval significantly fewer crossovers than expected. One-third of these crossovers occurred within 6 kilobases of the centromere. Approximately half of the exchanges were associated with gene conversion events. The minimum length of gene conversion tracts varied from 4 base pairs to more than 12 kilobases, and these tracts were nonuniformly distributed along the chromosome. We conclude that the chromosomal sequence or structure has a dramatic effect on meiotic recombination.

Authors
Symington, LS; Petes, TD
MLA Citation
Symington, LS, and Petes, TD. "Expansions and contractions of the genetic map relative to the physical map of yeast chromosome III." Mol Cell Biol 8.2 (February 1988): 595-604.
PMID
2832729
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
8
Issue
2
Publish Date
1988
Start Page
595
End Page
604

Meiotic recombination within the centromere of a yeast chromosome.

In order to examine the frequency of nonreciprocal recombination (gene conversion) within the centromere of the yeast chromosome, we constructed strains that contained heterozygous restriction sites in the conserved centromere sequences of chromosome III in addition to heterozygous markers flanking the centromere. One of these markers was the selectable URA3 gene, which was inserted less than one kb from the centromere. We found that meiotic conversion of the URA3 gene occurred at normal frequency (about 2% of unselected tetrads) and that more than one-third of these convertants coconverted the markers within the centromere. In addition, we observed tetrads in which conversion events extended through the centromere to include a marker on the opposite side from URA3. We conclude that meiotic conversion events occur within the centromere at rates similar to other genomic sequences.

Authors
Symington, LS; Petes, TD
MLA Citation
Symington, LS, and Petes, TD. "Meiotic recombination within the centromere of a yeast chromosome." Cell 52.2 (January 29, 1988): 237-240.
PMID
2830024
Source
pubmed
Published In
Cell
Volume
52
Issue
2
Publish Date
1988
Start Page
237
End Page
240

Recombination between repeated genes in microorganisms.

Authors
Petes, TD; Hill, CW
MLA Citation
Petes, TD, and Hill, CW. "Recombination between repeated genes in microorganisms." Annu Rev Genet 22 (1988): 147-168. (Review)
PMID
3071247
Source
pubmed
Published In
Annual Review of Genetics
Volume
22
Publish Date
1988
Start Page
147
End Page
168
DOI
10.1146/annurev.ge.22.120188.001051

MEIOTIC RECOMBINATION BETWEEN REPEATED GENES ON NONHOMOLOGOUS CHROMOSOMES.

Meiotic recombination events between repeated genes on nonhomologous chromosomes are examined. Initially, meiotic conversion was detected by tetrad dissection. Also, random spore analysis was used to detect such conversions. Conversion-associated reciprocal exchange is also discussed.

Authors
Jinks-Robertson, S; Petes, TD
MLA Citation
Jinks-Robertson, S, and Petes, TD. "MEIOTIC RECOMBINATION BETWEEN REPEATED GENES ON NONHOMOLOGOUS CHROMOSOMES." 3 (1987): 43-52.
Source
scival
Volume
3
Publish Date
1987
Start Page
43
End Page
52

Chromosomal translocations generated by high-frequency meiotic recombination between repeated yeast genes.

We have examined meiotic and mitotic recombination between repeated genes on nonhomologous chromosomes in the yeast Saccharomyces cerevisiae. The results of these experiments can be summarized in three statements. First, gene conversion events between repeats on nonhomologous chromosomes occur frequently in meiosis. The frequency of such conversion events is only 17-fold less than the analogous frequency of conversion between genes at allelic positions on homologous chromosomes. Second, meiotic and mitotic conversion events between repeated genes on nonhomologous chromosomes are associated with reciprocal recombination to the same extent as conversion between allelic sequences. The reciprocal exchanges between the repeated genes result in chromosomal translocations. Finally, recombination between repeated genes on nonhomologous chromosomes occurs much more frequently in meiosis than in mitosis.

Authors
Jinks-Robertson, S; Petes, TD
MLA Citation
Jinks-Robertson, S, and Petes, TD. "Chromosomal translocations generated by high-frequency meiotic recombination between repeated yeast genes." Genetics 114.3 (November 1986): 731-752.
PMID
3539696
Source
pubmed
Published In
Genetics
Volume
114
Issue
3
Publish Date
1986
Start Page
731
End Page
752

Most of the yeast genomic sequences are not essential for cell growth and division.

To determine the fraction of the yeast Saccharomyces cerevisiae genome that is required for normal cell growth and division, we constructed diploid strains that were heterozygous for random single disruptions. We monitored the effects of approximately 200 independent disruptions by sporulating the diploids and examining the phenotype of the resulting haploid strains. We found that only 12% of the disruptions were haploid-lethal, 14% resulted in slow growth, and an additional 4% were associated with some other new phenotype (such as an auxotrophic requirement). No obvious new phenotype was detected for 70% of the disruptions.

Authors
Goebl, MG; Petes, TD
MLA Citation
Goebl, MG, and Petes, TD. "Most of the yeast genomic sequences are not essential for cell growth and division." Cell 46.7 (September 26, 1986): 983-992.
PMID
3019561
Source
pubmed
Published In
Cell
Volume
46
Issue
7
Publish Date
1986
Start Page
983
End Page
992

Isolation and characterization of a Ty element inserted into the ribosomal DNA of the yeast Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae has about 30 to 50 copies of a transposable element Ty. Most of these elements are located at the 5' ends of protein coding sequences and are flanked by a 5 bp duplication. We report below an insertion of a Ty element into one of the repeated ribosomal RNA (rRNA) genes of yeast. The element is located between the 3' ends of the divergentally transcribed 37S and 5S rRNA's and is not flanked by a 5 bp duplication. In addition, one end of the Ty insertion is contiguous with a 306 bp deletion of the sequences of the rRNA gene. We find that this insertion, unlike most Ty insertions, is mitotically unstable.

Authors
Vincent, A; Petes, TD
MLA Citation
Vincent, A, and Petes, TD. "Isolation and characterization of a Ty element inserted into the ribosomal DNA of the yeast Saccharomyces cerevisiae." Nucleic Acids Res 14.7 (April 11, 1986): 2939-2949.
PMID
3008101
Source
pubmed
Published In
Nucleic Acids Research
Volume
14
Issue
7
Publish Date
1986
Start Page
2939
End Page
2949

Identification of yeast mutants with altered telomere structure.

The chromosomes of the yeast Saccharomyces cerevisiae terminate in a tract of simple-sequence DNA [poly(C1-3A)] that is several hundred base pairs long. We describe the identification of mutant yeast strains that have telomeric tracts that are shorter than normal. A genetic analysis of these strains indicates that these short telomeres are the result of single nuclear recessive mutations and that these mutations can be classified into two different complementation groups. The full expression of the mutant phenotype shows a very long lag (approximately equal to 150 cell divisions). From our analysis of these mutants as well as other data, we suggest that the duplication of the telomeric poly(C1-3A) tract involves two processes, semiconservative replication and untemplated terminal addition of nucleotides.

Authors
Lustig, AJ; Petes, TD
MLA Citation
Lustig, AJ, and Petes, TD. "Identification of yeast mutants with altered telomere structure." Proc Natl Acad Sci U S A 83.5 (March 1986): 1398-1402.
PMID
3513174
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
83
Issue
5
Publish Date
1986
Start Page
1398
End Page
1402

High-frequency meiotic gene conversion between repeated genes on nonhomologous chromosomes in yeast.

We have used a genetic system that allows detection of meiotic recombination events between repeated sequences on nonhomologous chromosomes in the yeast Saccharomyces cerevisiae. We have found that recombination between these sequences occurs at a frequency of about 0.5%, and the events observed were nonreciprocal (gene conversions). Surprisingly, the frequency of conversion between the repeated genes on nonhomologous chromosomes observed in this study is similar to that observed between allelic genes. This result is discussed in connection with the role of the synaptonemal complex in meiotic recombination and with the relationship between reciprocal and nonreciprocal recombination.

Authors
Jinks-Robertson, S; Petes, TD
MLA Citation
Jinks-Robertson, S, and Petes, TD. "High-frequency meiotic gene conversion between repeated genes on nonhomologous chromosomes in yeast." Proc Natl Acad Sci U S A 82.10 (May 1985): 3350-3354.
PMID
3889906
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
82
Issue
10
Publish Date
1985
Start Page
3350
End Page
3354

Genetic control of chromosome length in yeast.

The chromosomes of the yeast Saccharomyces cerevisiae terminate with sequences that have the form poly(C1-3-A). In this paper, we show that within an individual yeast strain all chromosomes end with tracts of poly(C1-3-A) of similar lengths; however, different strains can have tracts that vary in length by a factor of two. By a genetic analysis, we demonstrate that yeast cells have a mechanism that allows them to change rapidly the length of their chromosomes by altering the length of the poly(C1-3-A) tract.

Authors
Walmsley, RM; Petes, TD
MLA Citation
Walmsley, RM, and Petes, TD. "Genetic control of chromosome length in yeast." Proc Natl Acad Sci U S A 82.2 (January 1985): 506-510.
PMID
2982162
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
82
Issue
2
Publish Date
1985
Start Page
506
End Page
510

Long poly(A) tracts in the human genome are associated with the Alu family of repeated elements.

Long poly(dA).poly(dT) tracts (poly(A) tracts), regions of DNA containing at least 20 contiguous dA residues on one strand and dT residues on the complementary strand, are found in about 2 X 10(4) copies interspersed throughout the human genome. Using poly(dA).poly(dA) as a hybridization probe, we identified recombinant lambda phage that contained inserts of human DNA with poly(A) tracts. Three such tracts have been characterized by restriction mapping and sequence analysis. One major poly(A) tract is present within each insert and is composed of from 28 to 35 A residues. In each case, the poly(A) tract directly abuts the 3' end of the human Alu element, indicating that the major class of poly(A) tracts in the human genome is associated with this family of repeats. The poly(A) tracts are also adjacent to A-rich sequences and, in one case, to a polypurine tract, having the structure GA3-GA3-GA4-GA6-GA5-GA4. We suggest that repetitive cycles of unequal crossing over may give rise to both the long poly(A) and polypurine tracts observed in this study.

Authors
Lustig, AJ; Petes, TD
MLA Citation
Lustig, AJ, and Petes, TD. "Long poly(A) tracts in the human genome are associated with the Alu family of repeated elements." J Mol Biol 180.3 (December 15, 1984): 753-759.
PMID
6241262
Source
pubmed
Published In
Journal of Molecular Biology
Volume
180
Issue
3
Publish Date
1984
Start Page
753
End Page
759

Tandemly arranged variant 5S ribosomal RNA genes in the yeast Saccharomyces cerevisiae.

Most of the ribosomal RNA genes of the yeast Saccharomyces cerevisiae are about 9 kilobases (kb) in size and encode both the 35S rRNA (processed to produce the 25S, 18S, and 5.8S species) and 5S rRNA. These genes are arranged in a single tandem array of 100 repeats. Below, we present evidence that at the centromere-distal end of this array is a tandem arrangement of a different type of rRNA gene. Each of these repeats is 3.6 kb in length and encodes a single 5S rRNA. The coding sequence of this gene is different from that of the "normal" 5S gene in three positions located at the 3' end of the gene.

Authors
McMahon, ME; Stamenkovich, D; Petes, TD
MLA Citation
McMahon, ME, Stamenkovich, D, and Petes, TD. "Tandemly arranged variant 5S ribosomal RNA genes in the yeast Saccharomyces cerevisiae." Nucleic Acids Res 12.21 (November 12, 1984): 8001-8016.
PMID
6095183
Source
pubmed
Published In
Nucleic Acids Research
Volume
12
Issue
21
Publish Date
1984
Start Page
8001
End Page
8016

Gene conversion in the absence of reciprocal recombination.

Authors
Fink, GR; Petes, TD
MLA Citation
Fink, GR, and Petes, TD. "Gene conversion in the absence of reciprocal recombination." Nature 310.5980 (August 30, 1984): 728-729.
PMID
6472456
Source
pubmed
Published In
Nature
Volume
310
Issue
5980
Publish Date
1984
Start Page
728
End Page
729

Unusual DNA sequences associated with the ends of yeast chromosomes.

The genome of the yeast Saccharomyces cerevisiae, like those of other eukaryotes, contains multiple sequences that hybridize with a poly(GT) probe. We have shown previously that some of the sequences that hybridize with the poly(GT) probe are located near the tips of the yeast chromosomes. We report here that many of the remaining poly(GT)-hybridizing sequences are associated with a family of putative replication origins localized near the chromosome ends. These sequences have the general form poly(C1-3A), similar to sequences reported to occur at the tips of chromosomes in the accompanying paper. In addition to poly(C1-3A) tracts, yeast cells contain tracts of alternating C and A bases, similar to those seen in mammalian genomes. These results are used as the basis for a new model of telomere replication.

Authors
Walmsley, RW; Chan, CS; Tye, BK; Petes, TD
MLA Citation
Walmsley, RW, Chan, CS, Tye, BK, and Petes, TD. "Unusual DNA sequences associated with the ends of yeast chromosomes." Nature 310.5973 (July 12, 1984): 157-160.
PMID
6377091
Source
pubmed
Published In
Nature
Volume
310
Issue
5973
Publish Date
1984
Start Page
157
End Page
160

Genetic mapping of Ty elements in Saccharomyces cerevisiae.

We used transformation to insert a selectable marker at various sites in the Saccharomyces cerevisiae genome occupied by the transposable element Ty. The vector CV9 contains the LEU2+ gene and a portion of the repeated element Ty1-17. Transformation with this plasmid resulted in integration of the vector via a reciprocal exchange using homology at the LEU2 locus or at the various Ty elements that are dispersed throughout the S. cerevisiae genome. These transformants were used to map genetically sites of several Ty elements. The 24 transformants recovered at Ty sites define 19 distinct loci. Seven of these were placed on the genetic map. Two classes of Ty elements were identified in these experiments: a Ty1-17 class and Ty elements different from Ty1-17. Statistical analysis of the number of transformants at each class of Ty elements shows that there is preferential integration of the CV9 plasmid into the Ty1-17 class.

Authors
Klein, HL; Petes, TD
MLA Citation
Klein, HL, and Petes, TD. "Genetic mapping of Ty elements in Saccharomyces cerevisiae." Mol Cell Biol 4.2 (February 1984): 329-339.
PMID
6366520
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
4
Issue
2
Publish Date
1984
Start Page
329
End Page
339

Erratum: Unusual DNA sequences associated with the ends of yeast chromosomes (Nature (1984) 310 (157-160))

Authors
Walmsley, RM; Chan, CSM; Tye, BK; Petes, TD
MLA Citation
Walmsley, RM, Chan, CSM, Tye, BK, and Petes, TD. "Erratum: Unusual DNA sequences associated with the ends of yeast chromosomes (Nature (1984) 310 (157-160))." Nature 311.5983 (1984): 280--.
Source
scival
Published In
Nature
Volume
311
Issue
5983
Publish Date
1984
Start Page
280-
DOI
10.1038/311280b0

Recombination of plasmids into the Saccharomyces cerevisiae chromosome is reduced by small amounts of sequence heterogeneity.

As a model system for studying the properties of mitotic recombination in the yeast Saccharomyces cerevisiae, we have examined recombination between a recombinant plasmid (introduced into the S. cerevisiae cell by transformation) and homologous chromosomal loci. The recombinant plasmids used in these experiments contained S. cerevisiae rRNA genes. We found that the frequency of integrative recombination is sensitive to small amounts of sequence heterogeneity. In addition, the frequency and specificity of these recombination events are affected by the lengths of the interacting homologous DNA sequences.

Authors
Smolik-Utlaut, S; Petes, TD
MLA Citation
Smolik-Utlaut, S, and Petes, TD. "Recombination of plasmids into the Saccharomyces cerevisiae chromosome is reduced by small amounts of sequence heterogeneity." Mol Cell Biol 3.7 (July 1983): 1204-1211.
PMID
6350848
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
3
Issue
7
Publish Date
1983
Start Page
1204
End Page
1211

Is there left-handed DNA at the ends of yeast chromosomes?

Tracts of the alternating copolymer poly(dGdT . dCdA) have been observed in a variety of eukaryotes. Such tracts are of particular interest since homopolymers of this sequence can exist in vitro as left-handed Z form DNA. We have found that the yeast Saccharomyces cerevisiae contains at least 30 poly(GT) tracts at dispersed genomic locations. We show here that one subset of these tracts is located at the ends (telomeres) of the yeast chromosome. In addition, we show that poly(dGdT . dCdA) tracts are added to the ends of the extrachromosomal ribosomal DNA molecules of Tetrahymena when cloned in yeast. These data represent the first reported association between a homopolymeric sequence and a chromosome structure.

Authors
Walmsley, RM; Szostak, JW; Petes, TD
MLA Citation
Walmsley, RM, Szostak, JW, and Petes, TD. "Is there left-handed DNA at the ends of yeast chromosomes?." Nature 302.5903 (March 3, 1983): 84-86.
PMID
6338397
Source
pubmed
Published In
Nature
Volume
302
Issue
5903
Publish Date
1983
Start Page
84
End Page
86

Relationships among DNA sequences of the 1.3 kb EcoRI family of mouse DNA.

The genome of the mouse (Mus musculus) contains a family of repeated DNA sequences defined by a 1.3 kb EcoRI fragment. Restriction maps of ten cloned fragments from this family have been determined. The fragments were of seven different types, based on the patterns of digestion obtained with AvaII, HindIII, and TaqI restriction enzymes. These seven unique sets of sequences fell into two classes, as defined by the position of a single HindIII site. Portions of fragments from each of the two classes were sequenced. Although certain regions of the repeat were highly conserved between classes, there was more intraspecific sequence divergence among the sequenced regions than has been observed for the short interspersed Alu family of repeated sequences in mammals. Sequences of both HindIII classes were found to be present within the mouse X chromosome; we can conclude that both classes must also be present on other mouse chromosomes.

Authors
Dubnick, M; Chou, J; Petes, TD; Farber, RA
MLA Citation
Dubnick, M, Chou, J, Petes, TD, and Farber, RA. "Relationships among DNA sequences of the 1.3 kb EcoRI family of mouse DNA." J Mol Evol 19.2 (1983): 115-121.
PMID
6100837
Source
pubmed
Published In
Journal of Molecular Evolution
Volume
19
Issue
2
Publish Date
1983
Start Page
115
End Page
121

CHARACTERIZATION OF POLY DA POLY DT TRACTS IN THE HUMAN GENOME

Authors
LUSTIG, A; PETES, TD
MLA Citation
LUSTIG, A, and PETES, TD. "CHARACTERIZATION OF POLY DA POLY DT TRACTS IN THE HUMAN GENOME." AMERICAN JOURNAL OF HUMAN GENETICS 35.6 (1983): A178-A178.
Source
wos-lite
Published In
The American Journal of Human Genetics
Volume
35
Issue
6
Publish Date
1983
Start Page
A178
End Page
A178

Evidence that structural variants within the human delta-globin protein may reflect genetic interactions between the delta- and beta-globin genes.

Authors
Petes, TD
MLA Citation
Petes, TD. "Evidence that structural variants within the human delta-globin protein may reflect genetic interactions between the delta- and beta-globin genes." Am J Hum Genet 34.5 (September 1982): 820-823.
PMID
7124735
Source
pubmed
Published In
The American Journal of Human Genetics
Volume
34
Issue
5
Publish Date
1982
Start Page
820
End Page
823

Recombination between genes located on nonhomologous chromosomes in Saccharomyces cerevisiae.

We constructed strains of Saccharomyces cerevisiae that contained two different mutant alleles of either the leu2 gene or the ura3 gene. These repeated genes were located on chromosomes V and XII and the two leu2- alleles were located on chromosomes III and XII. Genetic interactions between the two mutant copies of a gene were detected by the generation of either Leu+ or Ura+ revertants. Both spontaneous and ultraviolet irradiation-induced revertants were examined. By genetic and physical analysis, we have shown that Leu+ or Ura+ revertants can arise by a variety of different genetic interactions. The most common type of genetic interaction is the nonreciprocal transfer of information from one repeat to the other. We also detected reciprocal recombination between repeated genes, resulting in reciprocally translocated chromosomes.

Authors
Mikus, MD; Petes, TD
MLA Citation
Mikus, MD, and Petes, TD. "Recombination between genes located on nonhomologous chromosomes in Saccharomyces cerevisiae." Genetics 101.3-4 (July 1982): 369-404.
PMID
6757052
Source
pubmed
Published In
Genetics
Volume
101
Issue
3-4
Publish Date
1982
Start Page
369
End Page
404

Intrachromosomal gene conversion and the maintenance of sequence homogeneity among repeated genes.

Intrachromosomal gene conversion is the non-reciprocal transfer of information between a pair of repeated genes on a single chromosome. This process produces eventual sequence homogeneity within a family of repeated genes. An evolutionary model for a single chromosome lineage was formulated and analyzed. Expressions were derived for the fixation probability, mean time to fixation or loss, and mean conditional fixation time for a variant repeat with an arbitrary initial frequency. It was shown that a small conversional advantage or disadvantage for the variant repeat (higher or lower probability of producing two variant genes by conversion than two wild-type genes) can have a dramatic effect on the probability of fixation. The results imply that intrachromosomal gene conversion can act sufficiently rapidly to be an important mechanism for maintaining sequence homogeneity among repeated genes.

Authors
Nagylaki, T; Petes, TD
MLA Citation
Nagylaki, T, and Petes, TD. "Intrachromosomal gene conversion and the maintenance of sequence homogeneity among repeated genes." Genetics 100.2 (February 1982): 315-337.
PMID
7106560
Source
pubmed
Published In
Genetics
Volume
100
Issue
2
Publish Date
1982
Start Page
315
End Page
337

Analysis of the junction between ribosomal RNA genes and single-copy chromosomal sequences in the yeast Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae has a single tandem array of 100 ribosomal RNA (rRNA) genes. We have cloned and characterized a junction between the centromere-distal end of this array and the adjacent single-copy chromosomal sequences. We have shown that the junction occurs within the nontranscribed region of the repeat. By mapping the junction, we have found that the 35S rRNA precursor is transcribed toward the centromere while the 5S rRNA is transcribed away from the centromere. We have also shown that different yeast strains can have different single-copy sequence at the junction.

Authors
Zamb, TJ; Petes, TD
MLA Citation
Zamb, TJ, and Petes, TD. "Analysis of the junction between ribosomal RNA genes and single-copy chromosomal sequences in the yeast Saccharomyces cerevisiae." Cell 28.2 (February 1982): 355-364.
PMID
6277511
Source
pubmed
Published In
Cell
Volume
28
Issue
2
Publish Date
1982
Start Page
355
End Page
364

Gene conversion between repeated genes

Authors
Petes, T; Fink, GR
MLA Citation
Petes, T, and Fink, GR. "Gene conversion between repeated genes." Nature 300.5889 (1982): 216-217.
PMID
6755261
Source
scival
Published In
Nature
Volume
300
Issue
5889
Publish Date
1982
Start Page
216
End Page
217
DOI
10.1038/300216a0

Intrachromosomal gene conversion in yeast.

We have shown that the yeast Saccharomyces cerevisiae has a mechanism by which information from one gene can be transferred non-reciprocally to a repeated copy of the gene on the same chromosome. This intrachromosomal gene conversion may be important in maintaining sequence homogeneity within families of repeated eukaryotic genes.

Authors
Klein, HL; Petes, TD
MLA Citation
Klein, HL, and Petes, TD. "Intrachromosomal gene conversion in yeast." Nature 289.5794 (January 15, 1981): 144-148.
PMID
7005693
Source
pubmed
Published In
Nature
Volume
289
Issue
5794
Publish Date
1981
Start Page
144
End Page
148

Unequal sister-strand recombination within yeast ribosomal DNA does not require the RAD 52 gene product

We have found that the RAD52 gene product, which is required for gene conversion and recombination in the yeast Saccharomyces cerevisiae, is not required for unequal mitotic sister-strand recombination. © 1981 Springer-Verlag.

Authors
Zamb, TJ; Petes, TD
MLA Citation
Zamb, TJ, and Petes, TD. "Unequal sister-strand recombination within yeast ribosomal DNA does not require the RAD 52 gene product." Current Genetics 3.2 (1981): 125-132.
PMID
24190058
Source
scival
Published In
Current Genetics
Volume
3
Issue
2
Publish Date
1981
Start Page
125
End Page
132
DOI
10.1007/BF00365716

Transposed LEU2 gene of Saccharomyces cerevisiae is regulated normally.

The repression of beta-isopropylmalate dehydrogenase, the LEU2 gene product, by leucine and leucine plus threonine was unaffected by the transposition of LEU2 from its original locus on chromosome III to a new locus within the ribosomal deoxyribonucleic acid gene cluster on chromosome XII. Since the expression of the LEU2 gene is probably controlled at a pretranslational level, we conclude that the recombinant plasmid used for transformation carries regulatory information in addition to LEU2 structural information.

Authors
Kohlhaw, GB; Hsu, YP; Lemmon, RD; Petes, TD
MLA Citation
Kohlhaw, GB, Hsu, YP, Lemmon, RD, and Petes, TD. "Transposed LEU2 gene of Saccharomyces cerevisiae is regulated normally." J Bacteriol 144.2 (November 1980): 852-855.
PMID
7000755
Source
pubmed
Published In
Journal of bacteriology
Volume
144
Issue
2
Publish Date
1980
Start Page
852
End Page
855

Unequal meiotic recombination within tandem arrays of yeast ribosomal DNA genes.

Recombinant DNA procedures and the yeast transformation technique were used to insert the yeast gene LEU 2 (coding for beta-isopropylmalate dehydrogenase) into the tandem array of ribosomal DNA genes of the yeast Saccharomyces cerevisiae. These insertions were shown by genetic and physical techniques to be unstable in meiosis. The meiotic instability was found to be the result of a high level of unequal recombination between ribosomal DNA gene clusters located on sister chromatids.

Authors
Petes, TD
MLA Citation
Petes, TD. "Unequal meiotic recombination within tandem arrays of yeast ribosomal DNA genes." Cell 19.3 (March 1980): 765-774.
PMID
6988084
Source
pubmed
Published In
Cell
Volume
19
Issue
3
Publish Date
1980
Start Page
765
End Page
774

Molecular genetics of yeast.

Authors
Petes, TD
MLA Citation
Petes, TD. "Molecular genetics of yeast." Annu Rev Biochem 49 (1980): 845-876. (Review)
PMID
6996573
Source
pubmed
Published In
Annual Review of Biochemistry
Volume
49
Publish Date
1980
Start Page
845
End Page
876
DOI
10.1146/annurev.bi.49.070180.004213

Evidence that the ribosomal DNA genes of yeast are not on chromosome I.

Several workers have reported that most of the ribosomal DNA genes (rDNA) of the yeast Saccharomyces cerevisiae are located on chromosome I. More recently, data indicating that the yeast rDNA genes are located on chromosome XII has been presented. In this report, we present additional evidence indicating that most of the yeast rDNA genes are not on chromosome I. Starting from a diploid yeast strain, we isolated ten strains which were monosomic (2n-1) for chromosome I. We found that each of these ten strains contained two copies of the rDNA-containing chromosome. In addition, we show that the earlier evidence indicating that the yeast rDNA genes were on chromosome I cannot be explained by a difference in the yeast strains which were used in the different experiments.

Authors
Petes, TD; Smolik-Utlaut, S
MLA Citation
Petes, TD, and Smolik-Utlaut, S. "Evidence that the ribosomal DNA genes of yeast are not on chromosome I." Mol Gen Genet 175.2 (September 1979): 187-193.
PMID
390314
Source
pubmed
Published In
Molecular & general genetics : MGG
Volume
175
Issue
2
Publish Date
1979
Start Page
187
End Page
193

Meiotic mapping of yeast ribosomal deoxyribonucleic acid on chromosome XII.

We have used meiotic mapping techniques to locate the position of the repeating ribosomal DNA (rDNA) genes of the yeast Saccharomyces cerevisiae. We found that the rDNA genes are located on the right arm of chromosome XII, approximately 45 map units centromere distal to the gene gal2. Together with mapping data from previous studies, this result suggests that the tandem array of rDNA genes contains at least two junctions with the non-rDNA of the yeast chromosome. In addition, we observed segregation patterns of the rDNA genes consistent with meiotic recombination within the rDNA gene tandem array in 3 of the 59 tetrads examined.

Authors
Petes, TD
MLA Citation
Petes, TD. "Meiotic mapping of yeast ribosomal deoxyribonucleic acid on chromosome XII." J Bacteriol 138.1 (April 1979): 185-192.
PMID
374364
Source
pubmed
Published In
Journal of bacteriology
Volume
138
Issue
1
Publish Date
1979
Start Page
185
End Page
192

Yeast ribosomal DNA genes are located on chromosome XII.

Two lines of experimental evidence indicate that the repeating ribosomal DNA (rDNA) genes of the yeast Saccharomyces cerevisiae are located on chromosome XII. First, the rDNA genes are linked mitotically to genes that have been previously mapped to chromosome XII. Second, yeast strains that have two copies of the chromosome containing the rDNA genes in every strain examined also have two copies of chromosome XII; this is not true for the other yeast chromosomes. These data also establish that in mitosis most of the rDNA genes in yeast are not extrachromosomal.

Authors
Petes, TD
MLA Citation
Petes, TD. "Yeast ribosomal DNA genes are located on chromosome XII." Proc Natl Acad Sci U S A 76.1 (January 1979): 410-414.
PMID
370829
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
76
Issue
1
Publish Date
1979
Start Page
410
End Page
414

Isolation and analysis of recombinant DNA molecules containing yeast DNA.

2500 recombinant plasmids containing insertions of yeast nuclear DNA have been cloned in Escherichia coli. It can be calculated that about 85% of the yeast genome is represented in this collection. The clones have been characterized by hybridization to purified RNA species. Of the 2000 clones examined, 75 contain insertions of yeast ribosomal DNA, 201 contain insertions of yeast tRNA genes, and 26 contain DNA sequences that are complementary to abundant mRNA species.

Authors
Petes, TD; Broach, JR; Wensink, PC; Hereford, LM; Fink, GR; Botstein, D
MLA Citation
Petes, TD, Broach, JR, Wensink, PC, Hereford, LM, Fink, GR, and Botstein, D. "Isolation and analysis of recombinant DNA molecules containing yeast DNA." Gene 4.1 (September 1978): 37-49.
PMID
365691
Source
pubmed
Published In
Gene
Volume
4
Issue
1
Publish Date
1978
Start Page
37
End Page
49

Location of the 5.8S rRNA gene of Saccharomyces cerevisiae.

Direct DNA sequence analysis of Saccharomyces cerevisiae ribosomal DNA cloned in an Escherichia coli plasmid revealed part of the structural gene for 5.8S rRNA at one end of a 700-base-pair EcoRI fragment. Taken with the previously established EcoRI restriction map of the ribosomal repeat unit, this sequence establishes that the yeast 5.8S RNA segment is located between the 18S and 28S segments in the 42S rRNA precursor and in the DNA which codes for it.

Authors
Skryabin, KG; Maxam, AM; Petes, TD; Hereford, L
MLA Citation
Skryabin, KG, Maxam, AM, Petes, TD, and Hereford, L. "Location of the 5.8S rRNA gene of Saccharomyces cerevisiae." J Bacteriol 134.1 (April 1978): 306-309.
PMID
348685
Source
pubmed
Published In
Journal of bacteriology
Volume
134
Issue
1
Publish Date
1978
Start Page
306
End Page
309

Characterization of two types of yeast ribosomal DNA genes.

The intragenic organization of ribosomal DNA from a diploid strain of Saccharomyces cerevisiae was analyzed by using recombinant DNA molecules constructed in vitro. Restriction analysis of the yeast ribosomal DNA with the EcoRI restriction enzyme indicated that eight restriction fragments were present in the ribosomal DNA of this strain: X' (1.87 X 10(6) daltons), A (1.77 X 10(6) daltons), B (1.48 X 10(6) daltons), C (1.22 X 10(6) daltons), D (0.39 X 10(6) daltons), E (0.36 X 10(6) daltons), F (0.22 X 10(6) daltons), and G (0.17 X 10(6) daltons). These fragments were distributed between two different types of ribosomal DNA genes, which had the restriction maps: (formula: see text) in which the underlined region shows the repeating unit. The diploid yeast strain contained approximately equal amounts of each of these two types of genes. The analysis of the recombinant DNA molecules also indicated that the yeast ribosomal genes are homogeneous and extensively clustered.

Authors
Petes, TD; Hereford, LM; Skryabin, KG
MLA Citation
Petes, TD, Hereford, LM, and Skryabin, KG. "Characterization of two types of yeast ribosomal DNA genes." J Bacteriol 134.1 (April 1978): 295-305.
PMID
348684
Source
pubmed
Published In
Journal of bacteriology
Volume
134
Issue
1
Publish Date
1978
Start Page
295
End Page
305

Simple Mendelian inheritance of the repeating yeast ribosomal DNA genes.

Authors
Petes, TD; Hereford, LM; Botstein, D
MLA Citation
Petes, TD, Hereford, LM, and Botstein, D. "Simple Mendelian inheritance of the repeating yeast ribosomal DNA genes." Cold Spring Harb Symp Quant Biol 42 Pt 2 (1978): 1201-1207.
PMID
354850
Source
pubmed
Published In
Cold Spring Harbor Laboratory: Symposia on Quantitative Biology
Volume
42 Pt 2
Publish Date
1978
Start Page
1201
End Page
1207

Simple Mendelian inheritance of the reiterated ribosomal DNA of yeast.

A diploid strain of yeast (Saccharomyces cerevisiae) was found to be heterozygous for two forms of the highly repetitious ribosomal DNA. These forms could be distinguished by the pattern of fragments produced after digestion with the site-specific restriction endonuclease EcoRI. The mode of inheritance of ribosomal DNA was determined by tetrad analysis. Of 14 tetrads analyzed, 12 clearly showed the ribosomal DNA forms segregating as a single Mendelian unit. The simplest interpretation of this result is that all of the approximately 100 copies of the ribosomal DNA genes of the yeast cell are located on one chromosome and that meiotic recombination within these genes is suppressed. Two of the 14 tetrads showed the segregation patterns expected as the result of mitotic recombination within the ribosomal DNA.

Authors
Petes, TD; Botstein, D
MLA Citation
Petes, TD, and Botstein, D. "Simple Mendelian inheritance of the reiterated ribosomal DNA of yeast." Proc Natl Acad Sci U S A 74.11 (November 1977): 5091-5095.
PMID
337310
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
74
Issue
11
Publish Date
1977
Start Page
5091
End Page
5095

Fiber autoradiography of replicating yeast DNA.

Authors
Petes, TD; Williamson, DH
MLA Citation
Petes, TD, and Williamson, DH. "Fiber autoradiography of replicating yeast DNA." Exp Cell Res 95.1 (October 1, 1975): 103-110.
PMID
1193142
Source
pubmed
Published In
Experimental Cell Research
Volume
95
Issue
1
Publish Date
1975
Start Page
103
End Page
110

Replicating circular DNA molecules in yeast.

The yeast Saccharomyces cerevisiae contains a class of small circular DNA molecules, approximately 2 mum in contour length (Sinclair et al., 1967). In this report, it is shown that these molecules replicate as double-branched circles, similar to those observed during replication of the bacteriophage lambda and Escherichia coli chromosomes. A normal rate of replication of these DNA circles requires the function of a nuclear gene, cdc 8.

Authors
Petes, TD; Williamson, DH
MLA Citation
Petes, TD, and Williamson, DH. "Replicating circular DNA molecules in yeast." Cell 4.3 (March 1975): 249-253.
PMID
1091361
Source
pubmed
Published In
Cell
Volume
4
Issue
3
Publish Date
1975
Start Page
249
End Page
253

Structure of DNA in DNA replication mutants of yeast.

Authors
Petes, TD; Newlon, CS
MLA Citation
Petes, TD, and Newlon, CS. "Structure of DNA in DNA replication mutants of yeast." Nature 251.5476 (October 18, 1974): 637-639.
PMID
4607806
Source
pubmed
Published In
Nature
Volume
251
Issue
5476
Publish Date
1974
Start Page
637
End Page
639

Altered rate of DNA replication in ageing human fibroblast cultures.

Authors
Petes, TD; Farber, RA; Tarrant, GM; Holliday, R
MLA Citation
Petes, TD, Farber, RA, Tarrant, GM, and Holliday, R. "Altered rate of DNA replication in ageing human fibroblast cultures." Nature 251.5474 (October 4, 1974): 434-436.
PMID
4423711
Source
pubmed
Published In
Nature
Volume
251
Issue
5474
Publish Date
1974
Start Page
434
End Page
436

Replication of yeast chromosomal DNA.

Authors
Newlon, CS; Petes, TD; Hereford, LM; Fangman, WL
MLA Citation
Newlon, CS, Petes, TD, Hereford, LM, and Fangman, WL. "Replication of yeast chromosomal DNA." Nature 247.5435 (January 4, 1974): 32-35.
PMID
4587640
Source
pubmed
Published In
Nature
Volume
247
Issue
5435
Publish Date
1974
Start Page
32
End Page
35

Yeast chromosomal DNA: size, structure, and replication.

Authors
Petes, TD; Newlon, CS; Byers, B; Fangman, WL
MLA Citation
Petes, TD, Newlon, CS, Byers, B, and Fangman, WL. "Yeast chromosomal DNA: size, structure, and replication." Cold Spring Harb Symp Quant Biol 38 (1974): 9-16.
PMID
4598644
Source
pubmed
Published In
Cold Spring Harbor Laboratory: Symposia on Quantitative Biology
Volume
38
Publish Date
1974
Start Page
9
End Page
16

Preferential synthesis of yeast mitochondrial DNA in alpha factor-arrested cells.

Authors
Petes, TD; Fangman, WL
MLA Citation
Petes, TD, and Fangman, WL. "Preferential synthesis of yeast mitochondrial DNA in alpha factor-arrested cells." Biochem Biophys Res Commun 55.3 (December 10, 1973): 603-609.
PMID
4586613
Source
pubmed
Published In
Biochemical and Biophysical Research Communications
Volume
55
Issue
3
Publish Date
1973
Start Page
603
End Page
609

Size and structure of yeast chromosomal DNA.

Electron microscopic analysis indicates that yeast nuclear DNA can be isolated as linear molecules ranging in size from 50 mum (1.2 x 10(8) daltons) to 355 mum (8.4 x 10(8) daltons). Analysis indicates the data is consistent with the hypothesis that each yeast chromosome contains a single, linear DNA duplex. Mitochondrial DNA molecules have a contour length of 21 +/- 2 mum and are mostly linear.

Authors
Petes, TD; Byers, B; Fangman, WL
MLA Citation
Petes, TD, Byers, B, and Fangman, WL. "Size and structure of yeast chromosomal DNA." Proc Natl Acad Sci U S A 70.11 (November 1973): 3072-3076.
PMID
4594033
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
70
Issue
11
Publish Date
1973
Start Page
3072
End Page
3076

Yeast chromosomal DNA: size, structure, and replication

Authors
Petes, TD; Newlon, CS; Byers, B; Fangman, WL
MLA Citation
Petes, TD, Newlon, CS, Byers, B, and Fangman, WL. "Yeast chromosomal DNA: size, structure, and replication." Symposia on Quantitative Biology Vol. 38 (1973): 9-16.
Source
scival
Published In
Symposia on Quantitative Biology
Volume
Vol. 38
Publish Date
1973
Start Page
9
End Page
16

Sedimentation properties of yeast chromosomal DNA.

Sedimentation analysis of nuclear DNA released from spheroplasts of the yeast Saccharomyces cerevisiae indicates that it has a number average molecular weight of 6.2 x 10(8). The chromosomal DNA molecules range in size from as small as 5 x 10(7) daltons to as large as 1.4 x 10(9) daltons. Based on these values and estimates of the total DNA content of the yeast nucleus, it is proposed that each yeast chromosome contains a single DNA duplex.

Authors
Petes, TD; Fangman, WL
MLA Citation
Petes, TD, and Fangman, WL. "Sedimentation properties of yeast chromosomal DNA." Proc Natl Acad Sci U S A 69.5 (May 1972): 1188-1191.
PMID
4556456
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
69
Issue
5
Publish Date
1972
Start Page
1188
End Page
1191
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