Mitosis-specific phosphorylation of Mis18α by Aurora B kinase enhances kinetochore recruitment of polo-like kinase 1

Abstract

Mis18 alpha, a component of Mis18 complex comprising of Mis18 alpha, Mis18 ss, and M18BP1, is known to localize at the centromere from late telophase to early G1 phase and plays a priming role in CENP-A deposition. Although its role in CENP-A deposition is well established, the other function of Mis18 alpha remains unknown. Here, we elucidate a new function of Mis18 alpha that is critical for the proper progression of cell cycle independent of its role in CENP-A deposition. We find that Aurora B kinase phosphorylates Mis18 alpha during mitosis not affecting neither centromere localization of Mis18 complex nor centromere loading of CENP-A. However, the replacement of endogenous Mis18 alpha by phosphorylation-defective mutant causes mitotic defects including micronuclei formation, chromosome misalignment, and chromosomal bridges. Together, our data demonstrate that Aurora B kinase-mediated mitotic phosphorylation of Mis18 alpha is a crucial event for faithful cell cycle progression through the enhanced recruitment of polo-like kinase 1 to the kinetochore.