1. Academic Validation
  2. Aurora B kinase activity-dependent and -independent functions of the chromosomal passenger complex in regulating sister chromatid cohesion

Aurora B kinase activity-dependent and -independent functions of the chromosomal passenger complex in regulating sister chromatid cohesion

  • J Biol Chem. 2019 Feb 8;294(6):2021-2035. doi: 10.1074/jbc.RA118.005978.
Qi Yi 1 Qinfu Chen 1 Haiyan Yan 1 Miao Zhang 1 Cai Liang 1 Xingfeng Xiang 1 Xuan Pan 1 Fangwei Wang 2
Affiliations

Affiliations

  • 1 From the Ministry of Education (MOE) Laboratory of Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • 2 From the Ministry of Education (MOE) Laboratory of Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China fwwang@zju.edu.cn.
Abstract

The chromosomal passenger complex (CPC) is a master regulator of mitosis. CPC consists of inner centromere protein (INCENP), Survivin, Borealin, and the kinase Aurora B and plays key roles in regulating kinetochore-microtubule attachments and spindle assembly checkpoint signaling. However, the role of CPC in sister chromatid cohesion, mediated by the cohesin complex, remains incompletely understood. Here, we show that Aurora B kinase activity contributes to centromeric cohesion protection partly through promoting kinetochore localization of the kinase Bub1. Interestingly, disrupting the interaction of INCENP with heterochromatin protein 1 (HP1) in HeLa cells selectively weakens cohesion at mitotic centromeres without detectably reducing the kinase activity of Aurora B. Thus, through this INCENP-HP1 interaction, the CPC also protects centromeric cohesion independently of Aurora B kinase activity. Moreover, the requirement for the INCENP-HP1 interaction in centromeric cohesion protection can be bypassed by tethering HP1 to centromeres or by depleting the cohesin release factor Wapl. We provide further evidence suggesting that the INCENP-HP1 interaction protects centromeric cohesion by promoting the centromere localization of Haspin, a protein kinase that antagonizes Wapl activity at centromeres. Taken together, this study identifies Aurora B kinase activity-dependent and -independent roles for the CPC in regulating centromeric cohesion during mitosis in human cells.

Keywords

Aurora B; Haspin; INCENP; cell cycle; centromere; chromosomal passenger complex; cohesin; heterochromatin protein 1; histone modification; kinetochore; mitosis; sister chromatid cohesion.

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