Reference - Detail
| 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 |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 5 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm3298 |