Disordered protein COSA-2 maintains crossover-specific repair compartments to ensure meiotic crossover maturation
Uebel, C. J.; Deng, D. Y.; Kim, Y.; Villeneuve, A. M.
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Faithful genome inheritance during meiosis relies on crossover repair of double-strand DNA breaks (DSBs) to connect homologous chromosomes and direct their proper segregation. The formation of crossover-specific recombination intermediates and accumulation of pro-crossover factors occurs at an extremely limited subset of DSB sites, necessitating that the subset of recombination sites designated to become crossovers reliably mature into crossovers. Here we identify C. elegans disordered protein COSA-2 as crucial for meiotic crossover maturation. COSA-2 abruptly concentrates at crossover intermediates in late pachytene nuclei, where it colocalizes and associates with other pro-crossover factors. COSA-2 is dispensable for early loading of crossover factors and for crossover designation, but is required for maintenance of pro-crossover factors at crossover-designated sites and for focal enrichment of factors initially distributed throughout the synaptonemal complex. We define a COSA-2 execution point during late pachytene wherein crossover intermediates transition from a vulnerable state (in which they require COSA-2 to avoid being dismantled) to a state where COSA-2 and local crossover-factor enrichment are no longer required to connect homologs. We propose that COSA-2 scaffolds privileged DNA repair compartments that promote crossover-factor accumulation and protect crossover intermediates until completion of repair, thereby ensuring that crossover-designated sites reliably mature into crossovers.
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