title: Dynamic phosphorylation of CENP-A at Ser68 orchestrates its cell-cycle-dependent deposition at centromeres.
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.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Zhouliang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Deng
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Junnan
authors.initials: J
authors.lastname: Fang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zichen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Shangze
authors.initials: S
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Linhui
authors.initials: L
authors.lastname: Zhai
authors.affiliation: 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.
authors.forename: Shengyi
authors.initials: S
authors.lastname: Peng
authors.affiliation: Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Jiemin
authors.initials: J
authors.lastname: Wong
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Guangshuo
authors.initials: G
authors.lastname: Ou
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Laboratory of Noncoding RNAs, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jizhong
authors.initials: J
authors.lastname: Lou
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Rui-Ming
authors.initials: RM
authors.lastname: Xu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: liguohong@sun5.ibp.ac.cn.
authors.forename: Guohong
authors.initials: G
authors.lastname: Li
mesh_terms: D001324:Autoantigens / Q000378:metabolism*; D015153:Blotting, Western; D016203:CDC2 Protein Kinase; D002453:Cell Cycle / Q000502:physiology*; D002503:Centromere / Q000502:physiology*; D000076247:Centromere Protein A; D002843:Chromatin / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008938:Mitosis / Q000502:physiology; D009707:Nucleosomes; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C524371:HJURP protein, human; D009707:Nucleosomes; D012694:Serine; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D054645:Protein Phosphatase 1