scholarly journals Mismatch repair impedes meiotic crossover interference

2018 ◽  
Author(s):  
Tim J. Cooper ◽  
Margaret R. Crawford ◽  
Laura J. Hunt ◽  
Marie-Claude Marsolier-Kergoat ◽  
Bertrand Llorente ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Dna Sequence ◽  
Meiotic Recombination ◽  
Molecular Level ◽  
Computational Modelling ◽  
Sequence Divergence ◽  
Global Distribution ◽  
Crossover Interference ◽  
Genome Wide ◽  
Meiotic Crossover

SummarySequence divergence, mediated by the anti-recombinogenic activity of mismatch repair (MMR), forms a potent barrier to meiotic recombination and in turn the formation of viable gametes1–5. However, exactly how MMR jeopardizes meiotic success is unclear. Here we utilize a combination ofS. cerevisiaegenetics, genome-wide mapping of recombination and computational modelling to demonstrate that MMR unexpectedly influences the global distribution of recombination through preferential suppression of interfering crossovers (COs) at regions of greater sequence divergence. As a result, inactivation of MMR not only increases the rate of recombination, as previously observed, but also, paradoxically, the strength of CO interference. Our observations reveal a new mechanism by which MMR spatially sculpts the meiotic landscape—linking CO control to the mechanisms that can reproductively isolate a population, and highlighting how genomes may become meiotically incompatible at the molecular level, dependent upon interactions of the primary DNA sequence.

scholarly journals Genome-Wide Analysis of Heteroduplex DNA in Mismatch Repair–Deficient Yeast Cells Reveals Novel Properties of Meiotic Recombination Pathways

PLoS Genetics ◽  
2011 ◽  
Vol 7 (9) ◽  
pp. e1002305 ◽  
Author(s):  
Emmanuelle Martini ◽  
Valérie Borde ◽  
Matthieu Legendre ◽  
Stéphane Audic ◽  
Béatrice Regnault ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Meiotic Recombination ◽  
Yeast Cells ◽  
Heteroduplex Dna ◽  
Genome Wide Analysis ◽  
Genome Wide

scholarly journals The Role of the Mismatch Repair Machinery in Regulating Mitotic and Meiotic Recombination Between Diverged Sequences in Yeast

Genetics ◽  
1999 ◽  
Vol 151 (4) ◽  
pp. 1299-1313 ◽  
Author(s):  
Wenliang Chen ◽  
Sue Jinks-Robertson
Keyword(s):  
Mismatch Repair ◽  
Meiotic Recombination ◽  
Type Strain ◽  
Wild Type Strain ◽  
Sequence Divergence ◽  
Rate Data ◽  
Wild Type ◽  
Recombination Rates ◽  
Sequence Identity

Abstract Nonidentical recombination substrates recombine less efficiently than do identical substrates in yeast, and much of this inhibition can be attributed to action of the mismatch repair (MMR) machinery. In this study an intron-based inverted repeat assay system has been used to directly compare the rates of mitotic and meiotic recombination between pairs of 350-bp substrates varying from 82% to 100% in sequence identity. The recombination rate data indicate that sequence divergence impacts mitotic and meiotic recombination similarly, although subtle differences are evident. In addition to assessing recombination rates as a function of sequence divergence, the endpoints of mitotic and meiotic recombination events involving 94%-identical substrates were determined by DNA sequencing. The endpoint analysis indicates that the extent of meiotic heteroduplex DNA formed in a MMR-defective strain is 65% longer than that formed in a wild-type strain. These data are consistent with a model in which the MMR machinery interferes with the formation and/or extension of heteroduplex intermediates during recombination.

scholarly journals Effect of DNA Sequence Divergence on Homologous Recombination as Analyzed by a Random-Walk Model

Genetics ◽  
1999 ◽  
Vol 153 (4) ◽  
pp. 1973-1988 ◽  
Author(s):  
Youhei Fujitani ◽  
Ichizo Kobayashi
Keyword(s):  
Random Walk ◽  
Homologous Recombination ◽  
Mismatch Repair ◽  
Dna Sequence ◽  
Recombination Frequency ◽  
Sequence Divergence ◽  
Random Walk Model ◽  
Homologous Region ◽  
Dna Duplexes ◽  
Rapid Drop

Abstract A point connecting a pair of homologous regions of DNA duplexes moves along the homology in a reaction intermediate of the homologous recombination. Formulating this movement as a random walk, we were previously successful at explaining the dependence of the recombination frequency on the homology length. Recently, the dependence of the recombination frequency on the DNA sequence divergence in the homologous region was investigated experimentally; if the methyl-directed mismatch repair (MMR) system is active, the logarithm of the recombination frequency decreases very rapidly with an increase of the divergence in a low-divergence regime. Beyond this regime, the logarithm decreases slowly and linearly with the divergence. This “very rapid drop-off” is not observed when the MMR system is defective. In this article, we show that our random-walk model can explain these data in a straightforward way. When a connecting point encounters a diverged base pair, it is assumed to be destroyed with a probability that depends on the level of MMR activity.

scholarly journals Exo1-protected DNA nicks direct crossover formation in meiosis

2021 ◽  
Author(s):  
Michael Gioia ◽  
Lisette Payero ◽  
Gianno Pannafino ◽  
Jun Jie Chen ◽  
Sagar Salim ◽  
...  
Keyword(s):  
Experimental Evidence ◽  
Mismatch Repair ◽  
Molecular Level ◽  
Holliday Junction ◽  
Crossing Over ◽  
Structural Elements ◽  
Crossover Interference ◽  
Double Holliday Junction ◽  
Dna Nicks ◽  
Null Mutants

In most sexually reproducing organisms crossing over between chromosome homologs during meiosis is critical for the viability of haploid gametes. Most crossovers that form in meiosis in budding yeast result from the biased resolution of double Holliday Junction (dHJ) intermediates. This dHJ resolution step involves the actions Rad2/XPG family nuclease Exo1 and the Mlh1- Mlh3 mismatch repair endonuclease. At present little is known about how these factors act in meiosis at the molecular level. Here we show that Exo1 promotes meiotic crossing over by protecting DNA nicks from ligation. We found that structural elements in Exo1 required for interactions with DNA, such as bending of DNA during nick/flap recognition, are critical for its role in crossing over. Consistent with these observations, meiotic expression of the Rad2/XPG family member Rad27 partially rescued the crossover defect in exo1 null mutants, and meiotic overexpression of Cdc9 ligase specifically reduced the crossover levels of exo1 DNA binding mutants to levels approaching the exo1 null. In addition, our work identified a role for Exo1 in crossover interference that appears independent of its resection activity. Together, these studies provide experimental evidence for Exo1 protected nicks being critical for the formation of meiotic crossovers and their distribution.

scholarly journals Natural variation identifies SNI1, the SMC5/6 component, as a modifier of meiotic crossover in Arabidopsis

2021 ◽  
Vol 118 (33) ◽  
pp. e2021970118
Author(s):  
Longfei Zhu ◽  
Nadia Fernández-Jiménez ◽  
Maja Szymanska-Lejman ◽  
Alexandre Pelé ◽  
Charles J. Underwood ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Genetic Analysis ◽  
Meiotic Recombination ◽  
Natural Variation ◽  
Genetic Interactions ◽  
Class I ◽  
Dna Helicases ◽  
Crossover Interference ◽  
Modifier Locus ◽  
Meiotic Crossover

The frequency and distribution of meiotic crossovers are tightly controlled; however, variation in this process can be observed both within and between species. Using crosses of two natural Arabidopsis thaliana accessions, Col and Ler, we mapped a crossover modifier locus to semidominant polymorphisms in SUPPRESSOR OF NPR1-1 INDUCIBLE 1 (SNI1), which encodes a component of the SMC5/6 complex. The sni1 mutant exhibits a modified pattern of recombination across the genome with crossovers elevated in chromosome distal regions but reduced in pericentromeres. Mutations in SNI1 result in reduced crossover interference and can partially restore the fertility of a Class I crossover pathway mutant, which suggests that the protein affects noninterfering crossover repair. Therefore, we tested genetic interactions between SNI1 and both RECQ4 and FANCM DNA helicases, which showed that additional Class II crossovers observed in the sni1 mutant are FANCM independent. Furthermore, genetic analysis of other SMC5/6 mutants confirms the observations of crossover redistribution made for SNI1. The study reveals the importance of the SMC5/6 complex in ensuring the proper progress of meiotic recombination in plants.

scholarly journals The megabase-scale crossover landscape is independent of sequence divergence

2022 ◽  
Author(s):  
Qichao Lian ◽  
Victor Solier ◽  
Birgit Walkemeier ◽  
Bruno Huettel ◽  
Korbinian Schneeberger ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Genetic Markers ◽  
Meiotic Recombination ◽  
Recombination Frequency ◽  
Sequence Divergence ◽  
Inbred Lines ◽  
Alternative Models ◽  
Genome Wide ◽  
Large Rearrangements ◽  
The Relationship

Meiotic recombination frequency varies along chromosomes and strongly correlates with sequence divergence. However, the causality underlying this correlation is unclear. To untangle the relationship between recombination landscapes and polymorphisms, we characterized the genome-wide recombination landscape in the absence of polymorphisms, using Arabidopsis thaliana homozygous inbred lines in which a few hundred genetic markers were introduced through mutagenesis. We found that megabase-scale recombination landscapes in inbred lines are strikingly similar to the recombination landscapes in hybrids, with the sole exception of heterozygous large rearrangements where recombination is prevented locally. In addition, we found that the megabase-scale recombination landscape can be accurately predicted by chromatin features. Our results show that polymorphisms are not causal for the shape of the megabase-scale recombination landscape, rather, favor alternative models in which recombination and chromatin shape sequence divergence across the genome.

The Budding Yeast Msh4 Protein Functions in Chromosome Synapsis and the Regulation of Crossover Distribution

Genetics ◽  
2001 ◽  
Vol 158 (3) ◽  
pp. 1013-1025 ◽  
Author(s):  
Janet E Novak ◽  
Petra B Ross-Macdonald ◽  
G Shirleen Roeder
Keyword(s):  
Mismatch Repair ◽  
Budding Yeast ◽  
Null Mutation ◽  
Crossing Over ◽  
Wild Type ◽  
Crossover Interference ◽  
Meiotic Chromosomes ◽  
Chromosome Synapsis ◽  
Protein Functions ◽  
Or Gene

AbstractThe budding yeast MSH4 gene encodes a MutS homolog produced specifically in meiotic cells. Msh4 is not required for meiotic mismatch repair or gene conversion, but it is required for wild-type levels of crossing over. Here, we show that a msh4 null mutation substantially decreases crossover interference. With respect to the defect in interference and the level of crossing over, msh4 is similar to the zip1 mutant, which lacks a structural component of the synaptonemal complex (SC). Furthermore, epistasis tests indicate that msh4 and zip1 affect the same subset of meiotic crossovers. In the msh4 mutant, SC formation is delayed compared to wild type, and full synapsis is achieved in only about half of all nuclei. The simultaneous defects in synapsis and interference observed in msh4 (and also zip1 and ndj1/tam1) suggest a role for the SC in mediating interference. The Msh4 protein localizes to discrete foci on meiotic chromosomes and colocalizes with Zip2, a protein involved in the initiation of chromosome synapsis. Both Zip2 and Zip1 are required for the normal localization of Msh4 to chromosomes, raising the possibility that the zip1 and zip2 defects in crossing over are indirect, resulting from the failure to localize Msh4 properly.

scholarly journals Poorly Repaired Mismatches in Heteroduplex DNA are Hyper-Recombinagenic in Saccharomyces cerevisiae

Genetics ◽  
1996 ◽  
Vol 142 (2) ◽  
pp. 407-416 ◽  
Author(s):  
P Manivasakam ◽  
Susan M Rosenberg ◽  
P J Hastings
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mismatch Repair ◽  
Genetic Markers ◽  
Meiotic Recombination ◽  
Repair System ◽  
Normal Allele ◽  
Heteroduplex Dna ◽  
Mismatch Repair System ◽  
Postmeiotic Segregation ◽  
System Operating

Abstract In yeast meiotic recombination, alleles used as genetic markers fall into two classes as regards their fate when incorporated into heteroduplex DNA. Normal alleles are those that form heteroduplexes that are nearly always recognized and corrected by the mismatch repair system operating in meiosis. High PMS (postmeiotic segregation) alleles form heteroduplexes that are inefficiently mismatch repaired. We report that placing any of several high PMS alleles very close to normal alleles causes hyperrecombination between these markers. We propose that this hyperrecombination is caused by the high PMS allele blocking a mismatch repair tract initiated from the normal allele, thus preventing corepair of the two alleles, which would prevent formation of recombinants. The results of three point crosses involving two PMS alleles and a normal allele suggest that high PMS alleles placed between two alleles that are normally corepaired block that corepair.

scholarly journals Crossover Interference in Saccharomyces cerevisiae Requires a TID1/RDH54- and DMC1-Dependent Pathway

Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1273-1286 ◽  
Author(s):  
Miki Shinohara ◽  
Kazuko Sakai ◽  
Akira Shinohara ◽  
Douglas K Bishop
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Meiotic Recombination ◽  
Strand Break ◽  
Tetrad Analysis ◽  
Yeast Saccharomyces Cerevisiae ◽  
Crossover Interference ◽  
Meiotic Progression ◽  
Invasion Stage ◽  
Strand Invasion ◽  
Dependent Pathway

Abstract Two RecA-like recombinases, Rad51 and Dmc1, function together during double-strand break (DSB)-mediated meiotic recombination to promote homologous strand invasion in the budding yeast Saccharomyces cerevisiae. Two partially redundant proteins, Rad54 and Tid1/Rdh54, act as recombinase accessory factors. Here, tetrad analysis shows that mutants lacking Tid1 form four-viable-spore tetrads with levels of interhomolog crossover (CO) and noncrossover recombination similar to, or slightly greater than, those in wild type. Importantly, tid1 mutants show a marked defect in crossover interference, a mechanism that distributes crossover events nonrandomly along chromosomes during meiosis. Previous work showed that dmc1Δ mutants are strongly defective in strand invasion and meiotic progression and that these defects can be partially suppressed by increasing the copy number of RAD54. Tetrad analysis is used to show that meiotic recombination in RAD54-suppressed dmc1Δ cells is similar to that in tid1; the frequency of COs and gene conversions is near normal, but crossover interference is defective. These results support the proposal that crossover interference acts at the strand invasion stage of recombination.

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