Lee Minkyoung, Kim Ik Soo, Park Koog Chan, Kim Jong-Seo, Baek Sung Hee, Kim Keun Il
Creative Research Initiatives Center for Chromatin Dynamics, Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea.
Department of Biological Sciences, Cellular Heterogeneity Research Center, Sookmyung Women's University, Seoul 04310, South Korea.
Oncotarget. 2017 Nov 27;9(2):1563-1576. doi: 10.18632/oncotarget.22707. eCollection 2018 Jan 5.
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.
Mis18α是由Mis18α、Mis18β和M18BP1组成的Mis18复合体的一个组成部分，已知它在末期晚期到G1期早期定位于着丝粒，并在CENP-A沉积中起引发作用。尽管其在CENP-A沉积中的作用已得到充分证实，但Mis18α的其他功能仍不清楚。在这里，我们阐明了Mis18α的一个新功能，该功能对于细胞周期的正常进行至关重要，且独立于其在CENP-A沉积中的作用。我们发现，Aurora B激酶在有丝分裂期间磷酸化Mis18α，这既不影响Mis18复合体的着丝粒定位，也不影响CENP-A的着丝粒加载。然而，用磷酸化缺陷型突变体替代内源性Mis18α会导致有丝分裂缺陷，包括微核形成、染色体排列错误和染色体桥。总之，我们的数据表明，Aurora B激酶介导的Mis18α有丝分裂磷酸化是通过增强polo样激酶1向动粒的募集来实现细胞周期忠实进行的关键事件。
