한빛사 논문
Jocelyn Haversata, Alexander Woglarb,c,1, Kayla Klatta, Chantal C. Akeribb,c, Victoria Robertsa, Shin-Yu Chend, Swathi Arurd, Anne M. Villeneuveb,c,2, and Yumi Kima,2
aDepartment of Biology, Johns Hopkins University, Baltimore, MD 21218 bDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305 cDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305; and dDepartment of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030
1Present address: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), CH1015, Lausanne, Switzerland.
2To whom correspondence may be addressed.
Abstract
Crossover formation is essential for proper segregation of homologous chromosomes during meiosis. Here, we show that Caenorhabditis elegans cyclin-dependent kinase 2 (CDK-2) partners with cyclin-like protein COSA-1 to promote crossover formation by promoting conversion of meiotic double-strand breaks into crossover–specific recombination intermediates. Further, we identify MutSγ component MSH-5 as a CDK-2 phosphorylation target. MSH-5 has a disordered C-terminal tail that contains 13 potential CDK phosphosites and is required to concentrate crossover–promoting proteins at recombination sites. Phosphorylation of the MSH-5 tail appears dispensable in a wild-type background, but when MutSγ activity is partially compromised, crossover formation and retention of COSA-1 at recombination sites are exquisitely sensitive to phosphosite loss. Our data support a model in which robustness of crossover designation reflects a positive feedback mechanism involving CDK-2–mediated phosphorylation and scaffold-like properties of the MSH5 C-terminal tail, features that combine to promote full recruitment and activity of crossover–promoting complexes.
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