Dynamic phosphorylation of CENP-A at Ser68 orchestrates its cell-cycle-dependent deposition at centromeres

Dev Cell. 2015 Jan 12;32(1):68-81. doi: 10.1016/j.devcel.2014.11.030.

Zhouliang Yu ¹, Xiang Zhou ², Wenjing Wang ², Wenqiang Deng ¹, Junnan Fang ¹, Hao Hu ¹, Zichen Wang ², Shangze Li ³, Lei Cui ⁴, Jing Shen ², Linhui Zhai ⁵, Shengyi Peng ⁶, Jiemin Wong ⁷, Shuo Dong ⁸, Zengqiang Yuan ⁹, Guangshuo Ou ², Xiaodong Zhang ³, Ping Xu ⁵, Jizhong Lou ¹⁰, Na Yang ², Ping Chen ², Rui-Ming Xu ², Guohong Li ¹¹

Affiliations

1 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
2 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
3 College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
4 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Laboratory of Noncoding RNAs, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
5 State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
6 University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
7 Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
8 Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
9 State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
10 Laboratory of Noncoding RNAs, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
11 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: [email protected].

PMID: 25556658 DOI: 10.1016/j.devcel.2014.11.030

Abstract

The H3 histone variant CENP-A is an epigenetic marker critical for the centromere identity and function. However, the precise regulation of the spatiotemporal deposition and propagation of CENP-A at centromeres during the cell cycle is still poorly understood. Here, we show that CENP-A is phosphorylated at Ser68 during early mitosis by CDK1. Our results demonstrate that phosphorylation of Ser68 eliminates the binding of CENP-A to the assembly factor HJURP, thus preventing the premature loading of CENP-A to the centromere prior to mitotic exit. Because CDK1 activity is at its minimum at the mitotic exit, the ratio of CDK1/PP1α activity changes in favor of Ser68 dephosphorylation, thus making CENP-A available for centromeric deposition by HJURP. Thus, we reveal that dynamic phosphorylation of CENP-A Ser68 orchestrates the spatiotemporal assembly of newly synthesized CENP-A at active centromeres during the cell cycle.

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