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

// Minkyoung Lee 1, * , Ik Soo Kim 1, * , Koog Chan Park 2 , Jong-Seo Kim 3 , Sung Hee Baek 1 , and Keun Il Kim 2 1 Creative Research Initiatives Center for Chromatin Dynamics, Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea 2 Department of Biological Sciences, Cellular Heterogeneity Research Center, Sookmyung Women’s University, Seoul 04310, South Korea 3 Center for RNA Research, Institute for Basic Science, Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea * These authors contributed equally to this work Correspondence to: Keun Il Kim, email: kikim@sookmyung.ac.kr Sung Hee Baek, email: sbaek@snu.ac.kr Keywords: Mis18α; Aurora B kinase; PLK1; mitosis-specific phosphorylation; polo box domain Received: August 06, 2017      Accepted: October 28, 2017      Published: November 27, 2017 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, we elucidate a new function of Mis18α 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 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 chromosomal bridges. Together, our 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 polo-like kinase 1 to the kinetochore.