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bioRxiv · 10.1101/2021.08.31.458431

Robust designation of meiotic crossover sites by CDK-2 through phosphorylation of the MutSγ complex

Haversat, J.·Woglar, A.·Klatt, K.·Akerib, C. C.·Roberts, V.·Salazar, C. C.·Chen, S.-Y.·Arur, S.·Villeneuve, A. M.·Kim, Y.
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Abstract

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 MutS{gamma} 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 MutS{gamma} 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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Haversat, J., Woglar, A., Klatt, K., Akerib, C. C., Roberts, V., Salazar, C. C., Chen, S.-Y., Arur, S., Villeneuve, A. M., Kim, Y.. 2021-09-01. Robust designation of meiotic crossover sites by CDK-2 through phosphorylation of the MutSγ complex. https://doi.org/10.1101/2021.08.31.458431

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