MYCBP ensures faithful chromosome segregation during mitosis by anchoring Astrin/SKAP to kinetochore.

Abstract

Proper kinetochore-microtubule (KT-MT) attachment is essential for faithful chromosome segregation during mitosis. The Astrin complex, localized at the outer kinetochore, stabilizes proper KT-MT attachments to ensure accurate chromosome alignment and segregation. MYCBP has been identified as a subunit of the Astrin complex, yet its mitotic function remains poorly illustrated. Here, we show that MYCBP displays diffuse cytoplasmic and nuclear distribution in interphase, but concentrates at spindles and kinetochores during metaphase and anaphase. Knockdown of MYCBP in HeLa and HCT116 cells resulted in metaphase alignment defects, mitotic arrest, and anaphase bridges. MYCBP depletion did not alter total Astrin or SKAP protein levels, but markedly reduced their kinetochore localization and compromised KT-MT attachment stability. MYCBP physically interacts with Astrin/SKAP via its N-terminus and specifies their localization to kinetochore. Importantly, Disruption of MYCBP-SKAP interaction by either a membrane-permeable competing peptide or point mutation abrogates accurate chromosome segregation, which recapitulated the MYCBP knockdown phenotypes. These findings reveal a key role for the MYCBP-SKAP interaction in achieving a stable kinetochore-microtubule interaction essential for faithful chromosome segregation.