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RRC ID 76186
Author Haversat J, Woglar A, Klatt K, Akerib CC, Roberts V, Chen SY, Arur S, Villeneuve AM, Kim Y.
Title Robust designation of meiotic crossover sites by CDK-2 through phosphorylation of the MutSγ complex.
Journal Proc Natl Acad Sci U S A
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.
Volume 119(21)
Pages e2117865119
Published 2022-5-24
DOI 10.1073/pnas.2117865119
PMID 35576467
PMC PMC9173770
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Chromosome Segregation Crossing Over, Genetic Cyclin-Dependent Kinase 2* / genetics Cyclin-Dependent Kinase 2* / metabolism DNA-Binding Proteins* / metabolism Meiosis* Phosphorylation Synaptonemal Complex* / genetics Synaptonemal Complex* / metabolism
Resource
C.elegans tm3298