Robust designation of meiotic crossover sites by CDK-2 through phosphorylation of the MutSγ complex.
Proc Natl Acad Sci U S A
; 119(21): e2117865119, 2022 05 24.
Article
em En
| MEDLINE
| ID: mdl-35576467
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 crossoverspecific 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 crossoverpromoting 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-2mediated phosphorylation and scaffold-like properties of the MSH5 C-terminal tail, features that combine to promote full recruitment and activity of crossoverpromoting complexes.
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Base de dados:
MEDLINE
Assunto principal:
Complexo Sinaptonêmico
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Proteínas de Caenorhabditis elegans
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Proteínas de Ligação a DNA
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Quinase 2 Dependente de Ciclina
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Meiose
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2022
Tipo de documento:
Article