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Down-regulation of Rad51 activity during meiosis in yeast prevents competition with Dmc1 for repair of double-strand breaks.
Liu, Yan; Gaines, William A; Callender, Tracy; Busygina, Valeria; Oke, Ashwini; Sung, Patrick; Fung, Jennifer C; Hollingsworth, Nancy M.
Affiliation
  • Liu Y; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
  • Gaines WA; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • Callender T; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
  • Busygina V; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • Oke A; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California, United States of America.
  • Sung P; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • Fung JC; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California, United States of America.
  • Hollingsworth NM; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
PLoS Genet ; 10(1): e1004005, 2014 Jan.
Article in En | MEDLINE | ID: mdl-24465215
ABSTRACT
Interhomolog recombination plays a critical role in promoting proper meiotic chromosome segregation but a mechanistic understanding of this process is far from complete. In vegetative cells, Rad51 is a highly conserved recombinase that exhibits a preference for repairing double strand breaks (DSBs) using sister chromatids, in contrast to the conserved, meiosis-specific recombinase, Dmc1, which preferentially repairs programmed DSBs using homologs. Despite the different preferences for repair templates, both Rad51 and Dmc1 are required for interhomolog recombination during meiosis. This paradox has recently been explained by the finding that Rad51 protein, but not its strand exchange activity, promotes Dmc1 function in budding yeast. Rad51 activity is inhibited in dmc1Δ mutants, where the failure to repair meiotic DSBs triggers the meiotic recombination checkpoint, resulting in prophase arrest. The question remains whether inhibition of Rad51 activity is important during wild-type meiosis, or whether inactivation of Rad51 occurs only as a result of the absence of DMC1 or checkpoint activation. This work shows that strains in which mechanisms that down-regulate Rad51 activity are removed exhibit reduced numbers of interhomolog crossovers and noncrossovers. A hypomorphic mutant, dmc1-T159A, makes less stable presynaptic filaments but is still able to mediate strand exchange and interact with accessory factors. Combining dmc1-T159A with up-regulated Rad51 activity reduces interhomolog recombination and spore viability, while increasing intersister joint molecule formation. These results support the idea that down-regulation of Rad51 activity is important during meiosis to prevent Rad51 from competing with Dmc1 for repair of meiotic DSBs.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cell Cycle Proteins / Saccharomyces cerevisiae Proteins / DNA-Binding Proteins / Rad51 Recombinase / DNA Breaks, Double-Stranded / Meiosis Language: En Journal: PLoS Genet Journal subject: GENETICA Year: 2014 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cell Cycle Proteins / Saccharomyces cerevisiae Proteins / DNA-Binding Proteins / Rad51 Recombinase / DNA Breaks, Double-Stranded / Meiosis Language: En Journal: PLoS Genet Journal subject: GENETICA Year: 2014 Document type: Article Affiliation country: