Evidence for short-patch mismatch repair in Saccharomyces cerevisiae

Coïc, Eric; Gluck, Laurence; Fabre, Francis

doi:10.1093/emboj/19.13.3408

Cited by 45 publications

(60 citation statements)

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“…In the first, Mlh1p and Msh2p curs. Both restorational and conversional mispair removal in the absence of Msh2p have been observed modulate strand invasion such that a greater proportion of the 3Ј-tail invades the homolog and/or a greater (Coic et al 2000), and the data presented here provide additional, albeit indirect, evidence for restorational proportion of heteroduplex DNA is formed upon strand capture. The Mer3p helicase has recently been demonmispair removal.…”

Section: Crossovers Map To Either Side Of the Non-mendelian Mapped Tosupporting

confidence: 52%

“…If SDSA prevails, some of the one-sided events may also be restored, thus LITERATURE CITED leaving no sign of a DSB repair event. In the absence of the Msh2p/Mlh1p nick-directed repair pathway, a (Coic et al 2000). Without strand form a complex that specifically binds to duplex oligonucleotides bias, there would be a 50% chance of a restoration.…”

Section: Crossovers Map To Either Side Of the Non-mendelian Mapped Tomentioning

confidence: 99%

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MLH1 and MSH2 Promote the Symmetry of Double-Strand Break Repair Events at the HIS4 Hotspot in Saccharomyces cerevisiae

et al. 2005

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Double-strand breaks (DSBs) initiate meiotic recombination. The DSB repair model predicts that both genetic markers spanning the DSB should be included in heteroduplex DNA and be detectable as nonMendelian segregations (NMS). In experiments testing this, a significant fraction of events do not conform to this prediction, as only one of the markers displays NMS (one-sided events). Two explanations have been proposed to account for the discrepancies between the predictions and experimental observations. One suggests that two-sided events are the norm but are "hidden" as heteroduplex repair frequently restores the parental configuration of one of the markers. Another explanation posits that one-sided events reflect events in which heteroduplex is formed predominantly on only one side of the DSB. In the absence of heteroduplex repair, the first model predicts that two-sided events would be revealed at the expense of one-sided events, while the second predicts no effect on the distribution of events when heteroduplex repair is lost. We tested these predictions by deleting the DNA mismatch repair genes MSH2 or MLH1 and analyzing the proportion of two-sided events. Unexpectedly, the results do not match the predictions of either model. In both mlh1⌬ and msh2⌬, the proportion of two-sided events is significantly decreased relative to wild type. These observations can be explained in one of two ways. Either Msh2p/ Mlh1p-independent mispair removal leads to restoration of one of the markers flanking the DSB site or Msh2p/Mlh1p actively promote two-sided events.

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Section: Crossovers Map To Either Side Of the Non-mendelian Mapped Tosupporting

confidence: 52%

Section: Crossovers Map To Either Side Of the Non-mendelian Mapped Tomentioning

confidence: 99%

MLH1 and MSH2 Promote the Symmetry of Double-Strand Break Repair Events at the HIS4 Hotspot in Saccharomyces cerevisiae

et al. 2005

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“…They are of two kinds-those whose values are preset by the model (nonadjustable parameters) and those that are specific to the HIS4 DSB hotspot and the markers in Hoffmann's strains (adjustable parameters). repair (Szostak et al 1983) or FC-biased ''shortpatch repair'' (Coïc et al 2000) d R, the probability that heteroduplex rejection in the pairing pathway (Chambers et al 1996;Goldfarb and Alani 2005) does not occur (see Appendix A) d m, the probability, specific for each marker, that mismatches in the pairing pathway are repaired (always to FC rather than 2:2)…”

Section: Resultsmentioning

confidence: 99%

“…The absence of MMR, by either mutation or use of poorly repaired palindromes, allows a second, unbiased mispair removal pathway to restore a proportion of heteroduplexes, leading to apparent one-sided events.'' This proposal suffers from several problems, one of which is that the short-patch system hypothesized by to be responsible for this unbiased MMR is claimed by its discoverers in yeast (Coïc et al 2000) to be biased against the marker on the invading strand, thus favoring FCs over restorations (and see Appendix A, Disparity between the two classes of HCs). Our model suggests, instead, that a traveling D-loop in the pairing pathway allows a mismatch created at invasion only a transient opportunity to enjoy MMR (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

A Two-Pathway Analysis of Meiotic Crossing Over and Gene Conversion in Saccharomyces cerevisiae

Stahl

Foss

2010

Genetics

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Several apparently paradoxical observations regarding meiotic crossing over and gene conversion are readily resolved in a framework that recognizes the existence of two recombination pathways that differ in mismatch repair, structures of intermediates, crossover interference, and the generation of noncrossovers. One manifestation of these differences is that simultaneous gene conversion on both sides of a recombination-initiating DNA double-strand break (''two-sidedness'') characterizes only one of the two pathways and is promoted by mismatch repair. Data from previous work are analyzed quantitatively within this framework, and a molecular model for meiotic double-strand break repair based on the concept of sliding D-loops is offered as an efficient scheme for visualizing the salient results from studies of crossing over and gene conversion, the molecular structures of recombination intermediates, and the biochemical competencies of the proteins involved. E UKARYOTES transit from the diplophase to the haplophase via meiosis, which is associated with a number of interrelated processes, including crossing over and gene conversion. These processes involve meiosisspecific, programmed DNA double-strand breaks (DSBs) and their repair (DSBr). DSBr, in turn, is associated with mismatched base pairs and their rectification, referred to as ''mismatch repair '' or MMR (Bishop et al. 1987). Current efforts to accommodate both the genetic and molecular phenomena associated with meiotic DSBr in yeast (Saccharomyces cerevisiae) have been thoroughly reviewed (e.g., Hollingsworth and Brill 2004;Hoffmann and Borts 2004;Surtees et al. 2004;Hunter 2007;Berchowitz and Copenhaver 2010), but none of the reviews commits to an overall picture with quantitative predictions. This work aims to remedy that lack. Specifically, we have made use of salient published studies to develop, step-by-step, a comprehensive model of meiotic DSBr and MMR. The main features of this model are summarized in Table 1. RESULTSFor readers who are unfamiliar with yeast genetics and/or the known details of MMR, we begin by reviewing (1) the basic principles and vocabulary of tetrad analysis in yeast, which expose the products of individual acts of meiosis, (2) the DSBr model of Szostak et al. (1983) as modified by Sun et al. (1991), which has provided a basic molecular interpretation of meiotic recombination, and (3) the known roles of mismatchrepair proteins such as Msh2 and Mlh1.Relative frequencies of tetrad types provide measures of linkage distance and crossover interference: Consider a population of diploid yeast cells heterozygous for two linked sites, A/a and D/d. When meiosis proceeds without a hitch, the resulting tetrads each contain four viable haploid spores. Because the genotypes of the spores are identifiable by the phenotypes of the colonies they give rise to, each spore in the tetrad can be characterized as a crossover or a noncrossover with respect to sites A/a and D/d. When the A/a and D/d sites are closely linked, the most frequent ...

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“…Such observations might indicate either that the heteroduplex extends to distal positions even in a MutL wild-type context or that the absence of mismatch repair leads to an increase in heteroduplex length. Furthermore, the detection of molecules with mosaic structures suggests that heteroduplex DNA has been repaired in a noncontinuous way, possibly by an alternative repair pathway, such as the short patch repair pathways described in msh2 and pms2 mutant strains of S. cerevisiae and S. pombe (Fleck et al 1999;Coic et al 2000;Hoffmann et al 2005) and in msh6 mutants of Drosophila melanogaster (Radford et al 2007b). …”

Section: Absent In Mlh3mentioning

confidence: 99%

Distinct Functions of MLH3 at Recombination Hot Spots in the Mouse

et al. 2008

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The four mammalian MutL homologs (MLH1, MLH3, PMS1, and PMS2) participate in a variety of events, including postreplicative DNA repair, prevention of homeologous recombination, and crossover formation during meiosis. In this latter role, MLH1-MLH3 heterodimers predominate and are essential for prophase I progression. Previous studies demonstrated that mice lacking Mlh1 exhibit a 90% reduction in crossing over at the Psmb9 hot spot while noncrossovers, which do not result in exchange of flanking markers but arise from the same double-strand break event, are unaffected. Using a PCR-based strategy that allows for detailed analysis of crossovers and noncrossovers, we show here that Mlh3 À/À exhibit a 85-94% reduction in the number of crossovers at the Psmb9 hot spot. Most of the remaining crossovers in Mlh3 À/À meiocytes represent simple exchanges similar to those seen in wild-type mice, with a small fraction (6%) representing complex events that can extend far from the initiation zone. Interestingly, we detect an increase of noncrossovers in Mlh3 À/À spermatocytes. These results suggest that MLH3 functions predominantly with MLH1 to promote crossovers, while noncrossover events do not require these activities. Furthermore, these results indicate that $10% of crossovers in the mouse are independent of MLH3, suggesting the existence of alternative crossover pathways in mammals. M EIOTIC recombination between homologous chromosomes during prophase I can result in both crossover (CO) and noncrossover (NCO) products. Most, if not all, of these events are initiated by the same double-strand break (DSB) event induced by SPO11, a conserved protein sharing sequence similarities with the catalytic subunit of TopoVI, a type II DNA topoisomerase from archae (reviewed in Keeney and Neale 2006), but are processed through distinct and highly conserved molecular pathways, the details of which remain to be elucidated fully in mammals.

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Evidence for short-patch mismatch repair in Saccharomyces cerevisiae

Cited by 45 publications

References 46 publications

MLH1 and MSH2 Promote the Symmetry of Double-Strand Break Repair Events at the HIS4 Hotspot in Saccharomyces cerevisiae

MLH1 and MSH2 Promote the Symmetry of Double-Strand Break Repair Events at the HIS4 Hotspot in Saccharomyces cerevisiae

A Two-Pathway Analysis of Meiotic Crossing Over and Gene Conversion in Saccharomyces cerevisiae

Distinct Functions of MLH3 at Recombination Hot Spots in the Mouse

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