title: Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1.
abstract: During meiosis, programmed double strand breaks (DSBs) are repaired preferentially between homologs to generate crossovers that promote proper chromosome segregation at Meiosis I. In many organisms, there are two strand exchange proteins, Rad51 and the meiosis-specific Dmc1, required for interhomolog (IH) bias. This bias requires the presence, but not the strand exchange activity of Rad51, while Dmc1 is responsible for the bulk of meiotic recombination. How these activities are regulated is less well established. In dmc1Δ mutants, Rad51 is actively inhibited, thereby resulting in prophase arrest due to unrepaired DSBs triggering the meiotic recombination checkpoint. This inhibition is dependent upon the meiosis-specific kinase Mek1 and occurs through two different mechanisms that prevent complex formation with the Rad51 accessory factor Rad54: (i) phosphorylation of Rad54 by Mek1 and (ii) binding of Rad51 by the meiosis-specific protein Hed1. An open question has been why inhibition of Mek1 affects Hed1 repression of Rad51. This work shows that Hed1 is a direct substrate of Mek1. Phosphorylation of Hed1 at threonine 40 helps suppress Rad51 activity in dmc1Δ mutants by promoting Hed1 protein stability. Rad51-mediated recombination occurring in the absence of Hed1 phosphorylation results in a significant increase in non-exchange chromosomes despite wild-type levels of crossovers, confirming previous results indicating a defect in crossover assurance. We propose that Rad51 function in meiosis is regulated in part by the coordinated phosphorylation of Rad54 and Hed1 by Mek1.
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Callender
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 3244, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 3244, Paris, France.
authors.forename: Raphaelle
authors.identifier: 0000-0001-9685-7161
authors.initials: R
authors.lastname: Laureau
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Lihong
authors.identifier: 0000-0003-0086-8857
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Xiangyu
authors.identifier: 0000-0002-4284-8507
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Gene Regulation in Health and Disease and Department of Biological Sciences, Cleveland State University, Cleveland, Ohio, United States of America.
authors.forename: Rima
authors.identifier: 0000-0003-3206-4108
authors.initials: R
authors.lastname: Sandhu
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Saif
authors.initials: S
authors.lastname: Laljee
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Sai
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Ray T
authors.initials: RT
authors.lastname: Suhandynata
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Evelyn
authors.identifier: 0000-0002-4474-8761
authors.initials: E
authors.lastname: Prugar
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: William A
authors.initials: WA
authors.lastname: Gaines
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: YoungHo
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: Center for Gene Regulation in Health and Disease and Department of Biological Sciences, Cleveland State University, Cleveland, Ohio, United States of America.
authors.forename: G Valentin
authors.initials: GV
authors.lastname: Börner
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 3244, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 3244, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Nicolas
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Neiman
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Nancy M
authors.identifier: 0000-0003-3300-6444
authors.initials: NM
authors.lastname: Hollingsworth
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D020090:Chromosome Segregation / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D059765:Homologous Recombination / Q000235:genetics*; D048369:MAP Kinase Kinase 1 / Q000235:genetics*; D008540:Meiosis / Q000235:genetics; D008938:Mitosis / Q000235:genetics; D050505:Mutant Proteins / Q000235:genetics; D010766:Phosphorylation; D051135:Rad51 Recombinase / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C513033:DMC1 protein, S cerevisiae; D004268:DNA-Binding Proteins; C000616116:Hed1 protein, S cerevisiae; D050505:Mutant Proteins; D029701:Saccharomyces cerevisiae Proteins; D048369:MAP Kinase Kinase 1; D051135:Rad51 Recombinase; C075468:RAD54 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes