title: Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair.
abstract: Faithful meiotic chromosome segregation and fertility require meiotic recombination between homologous chromosomes rather than the equally available sister chromatid, a bias that in Saccharomyces cerevisiae depends on the meiotic kinase, Mek1. Mek1 is thought to mediate repair template bias by specifically suppressing sister-directed repair. Instead, we found that when Mek1 persists on closely paired (synapsed) homologues, DNA repair is severely delayed, suggesting that Mek1 suppresses any proximal repair template. Accordingly, Mek1 is excluded from synapsed homologues in wild-type cells. Exclusion requires the AAA+-ATPase Pch2 and is directly coupled to synaptonemal complex assembly. Stage-specific depletion experiments further demonstrate that DNA repair in the context of synapsed homologues requires Rad54, a repair factor inhibited by Mek1. These data indicate that the sister template is distinguished from the homologue primarily by its closer proximity to inhibitory Mek1 activity. We propose that once pairing or synapsis juxtaposes homologues, exclusion of Mek1 is necessary to avoid suppression of all templates and accelerate repair progression.
authors: Department of Biology, New York University, New York, New York, United States of America.
authors: Vijayalakshmi V
authors: VV
authors: Subramanian
authors: Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, Connecticut, United States of America.
authors: Amy J
authors: AJ
authors: MacQueen
authors: Department of Biology, New York University, New York, New York, United States of America.
authors: Gerben
authors: G
authors: Vader
authors: Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
authors: Miki
authors: M
authors: Shinohara
authors: Institut Curie/Centre de Recherche, CNRS, UMR3664, Paris, France.
authors: Aurore
authors: A
authors: Sanchez
authors: Institut Curie/Centre de Recherche, CNRS, UMR3664, Paris, France.
authors: Valérie
authors: V
authors: Borde
authors: Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
authors: Akira
authors: A
authors: Shinohara
authors: Department of Biology, New York University, New York, New York, United States of America.
authors: Andreas
authors: A
authors: Hochwagen
mesh_terms: D023902:Chromosome Pairing; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D008540:Meiosis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; C528119:Pch2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C090118:Zip1 protein, S cerevisiae; D048369:MAP Kinase Kinase 1; C075468:RAD54 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes