세포분열 과정에서의 Mis18α 인산화에 대한 기능 연구

Abstract

Mis18α, a component of Mis18 complex comprising of Mis18α, Mis18β, 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 Mis18α remains unknown. Here, I elucidate a new function of Mis18α that is critical for the proper progression of cell cycle independent of its role in CENP-A deposition. I find that Aurora B kinase phosphorylates Mis18α during mitosis not affecting neither centromere localization of Mis18 complex nor centromere loading of CENP-A. However, the replacement of endogenous Mis18α by phosphorylation-defective mutant causes mitotic defects including micronuclei formation, chromosome misalignment, and the chromatin bridges or lagging chromatids. Interestingly, PLK1, another mitotic kinase, shows decreased recruitment in Mis18α phosphorylation-defective cell lines. PBD of PLK1 recognizes Mis18α phosphorylation so that its kinetochore recruitment can be enhanced. Together, my data demonstrate that Aurora B kinase-mediated mitotic phosphorylation of Mis18α is a crucial event for faithful cell cycle progression through the enhanced recruitment of PLK1 to the kinetochore.