title: Controlling meiotic recombinational repair - specifying the roles of ZMMs, Sgs1 and Mus81/Mms4 in crossover formation.
abstract: Crossovers (COs) play a critical role in ensuring proper alignment and segregation of homologous chromosomes during meiosis. How the cell balances recombination between CO vs. noncrossover (NCO) outcomes is not completely understood. Further lacking is what constrains the extent of DNA repair such that multiple events do not arise from a single double-strand break (DSB). Here, by interpreting signatures that result from recombination genome-wide, we find that synaptonemal complex proteins promote crossing over in distinct ways. Our results suggest that Zip3 (RNF212) promotes biased cutting of the double Holliday-junction (dHJ) intermediate whereas surprisingly Msh4 does not. Moreover, detailed examination of conversion tracts in sgs1 and mms4-md mutants reveal distinct aberrant recombination events involving multiple chromatid invasions. In sgs1 mutants, these multiple invasions are generally multichromatid involving 3-4 chromatids; in mms4-md mutants the multiple invasions preferentially resolve into one or two chromatids. Our analysis suggests that Mus81/Mms4 (Eme1), rather than just being a minor resolvase for COs is crucial for both COs and NCOs in preventing chromosome entanglements by removing 3'- flaps to promote second-end capture. Together our results force a reevaluation of how key recombination enzymes collaborate to specify the outcome of meiotic DNA repair.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Center of Reproductive Sciences, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Oke
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Center of Reproductive Sciences, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Carol M
authors.initials: CM
authors.lastname: Anderson
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Center of Reproductive Sciences, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Phoebe
authors.initials: P
authors.lastname: Yam
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Center of Reproductive Sciences, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Fung
mesh_terms: D002842:Chromatids / Q000378:metabolism; D020090:Chromosome Segregation; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D045566:DNA, Cruciform / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D045585:Flap Endonucleases / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis; D009154:Mutation; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D045566:DNA, Cruciform; D004268:DNA-Binding Proteins; C091158:MSH4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D044767:Ubiquitin-Protein Ligases; D004720:Endonucleases; D045585:Flap Endonucleases; C411624:MUS81 protein, S cerevisiae; C112337:MMS4 protein, S cerevisiae; C090472:SGS1 protein, S cerevisiae; D053484:RecQ Helicases; C523917:Zip3 protein, S cerevisiae