Robust designation of meiotic crossover sites by CDK-2 through phosphorylation of the MutSγ complex
bioRxiv (Cold Spring Harbor Laboratory)(2021)
摘要
SUMMARY Crossover formation is essential for proper segregation of homologous chromosomes during meiosis. Here we show that C. elegans Cyclin-dependent kinase 2 (CDK-2) forms a complex with cyclin-like protein COSA-1 and supports crossover formation by promoting conversion of meiotic double-strand breaks (DSBs) 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 CDK-2/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 MSH-5 C-terminal tail, features that combine to promote full recruitment and activity of crossover-promoting complexes.
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关键词
meiotic crossover sites,phosphorylation
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