Aurora B promotes the CENP-T-CENP-W interaction to guide accurate chromosome segregation in mitosis

J Mol Cell Biol. 2024 Jan 10:mjae001. doi: 10.1093/jmcb/mjae001. Online ahead of print.

Abstract

Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules. Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network (CCAN) during chromosome segregation. CCAN contains 16 subunits, including CENP-W and CENP-T. However, the molecular recognition and mitotic regulation of the CCAN assembly remain elusive. Here, we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T. Aurora B phosphorylates CENP-W at Thr60, which enhances the interaction between CENP-W and CENP-T to ensure robust metaphase chromosome alignment and accurate chromosome segregation in mitosis. These findings delineate a conserved signaling cascade that integrates protein phosphorylation with CCAN integrity for the maintenance of genomic stability.

Keywords: Aurora B; CENP-T; CENP-W; kinetochore; mitosis; phosphorylation.