title: Mph1 requires mismatch repair-independent and -dependent functions of MutSalpha to regulate crossover formation during homologous recombination repair.
abstract: In budding yeast the DNA helicase Mph1 prevents genome rearrangements during ectopic homologous recombination (HR) by suppressing the formation of crossovers (COs). Here we show that during ectopic HR repair, the anti-CO function of Mph1 is intricately associated with the mismatch repair (MMR) factor, MutSalpha. In particular, during HR repair using a completely homologous substrate, we reveal an MMR-independent function of MutSalpha in generating COs that is specifically antagonized by Mph1, but not Sgs1. In contrast, both Mph1 and MutSalpha are required to efficiently suppress COs in the presence of a homeologous substrate. Mph1 acts redundantly with Sgs1 in this respect since mph1Delta sgs1Delta double mutant cells pheno-copy MutSalpha mutants and completely fail to discriminate homologous and homeologous sequences during HR repair. However, this defect of mph1Delta sgs1Delta cells is not due to an inability to carry out MMR but rather is accompanied by elevated levels of gene conversion (GC) and bi-directional GC tracts specifically in non-crossover products. Models describing how Mph1, MutSalpha and Sgs1 act in concert to suppress genome rearrangements during ectopic HR repair are discussed.
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington Oxford, OX3 9DS, UK.
authors.forename: Ye Dee
authors.initials: YD
authors.lastname: Tay
authors.forename: Julie M
authors.initials: JM
authors.lastname: Sidebotham
authors.forename: Leonard
authors.initials: L
authors.lastname: Wu
mesh_terms: D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D053843:DNA Mismatch Repair; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005785:Gene Conversion; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D053484:RecQ Helicases / Q000235:genetics; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C098790:MSH6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C491240:MPH1 protein, S cerevisiae; C090472:SGS1 protein, S cerevisiae; C489751:MSH2 protein, S cerevisiae; D051718:MutS Homolog 2 Protein; D053484:RecQ Helicases; D053487:DEAD-box RNA Helicases