Cohesin-mediated stabilization of the CCAN complex at kinetochores in mitosis

Le résumé fourni par la source

The constitutive centromere-associated network (CCAN) of the inner kinetochore links CENP-A-containing nucleosomes of the centromere to the outer kinetochore, ensuring accurate chromosome segregation during mitosis. CCAN binding at the centromere is stabilized upon mitotic entry, but the underlying mechanisms remain unclear. Here, we demonstrate that cohesin is essential for CCAN stability. The chromosomal passenger complex (CPC), independently of its kinase subunit Aurora B, regulates cohesin-mediated CCAN stability via heterochromatin protein-1 (HP1), Haspin kinase, and phosphorylation of the cohesin-release factor WAPL, which weakens WAPL's affinity for PDS5B. While cohesin depletion disrupts CCAN stability, neither separase-mediated cohesin cleavage nor depletion of the cohesion-essential Esco2 acetyltransferase affects CCAN stability, indicating that cohesin stabilizes the CCAN independently of sister chromatid cohesion. Furthermore, we show that WAPL phosphorylation maintains a centromere-proximal pool of cohesin and promotes the formation of the primary constriction. These findings establish a non-cohesive function of cohesin in stabilizing the CCAN during mitosis and suggest that cohesin-mediated organization of centromeric chromatin strengthens kinetochore engagement to ensure faithful chromosome segregation.

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