Ser68 phosphoregulation is essential for CENP-A deposition,centromere function and viability in mice  

作　　者：Yuting Liu Kehui Wang Li Huang Jicheng Zhao Xinpeng Chen Qiang Wu Zhouliang Yu Guohong Li 

机构地区：[1]National Laboratory of Bio-macromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]Center for Disease Control and Prevention of PLA,Beijing 100071,China [4]College of Life Sciences,Hubei Normal University,Huangshi 435002,China [5]Center for Comparative Biomedicine,Key Laboratory of Systems Biomedicine(Ministry of Education),Institute of Systems Biomedicine,Shanghai Jiao Tong University,Shanghai 200240,China

出　　处：《Science China(Life Sciences)》2022年第9期1881-1889,共9页中国科学（生命科学英文版）

基　　金：This work was supported by the Ministry of Science and Technology of China(2017YFA0504202 and 2019YFA0508903);the National Natural Science Foundation of China(31991161 and 32070604);the Beijing Municipal Science and Technology Committee(Z201100005320013);HHMI International Research Scholar grant(55008737).

摘　　要：Centromere identity is defined by nucleosomes containing CENP-A,a histone H3 variant.The deposition of CENP-A at centromeres is tightly regulated in a cell-cycle-dependent manner.We previously reported that the spatiotemporal control of centromeric CENP-A incorporation is mediated by the phosphorylation of CENP-A Ser68.However,a recent report argued that Ser68 phosphoregulation is dispensable for accurate CENP-A loading.Here,we report that the substitution of Ser68 of endogenous CENP-A with either Gln68 or Glu68 severely impairs CENP-A deposition and cell viability.We also find that mice harboring the corresponding mutations are lethal.Together,these results indicate that the dynamic phosphorylation of Ser68 ensures cell-cycle-dependent CENP-A deposition and cell viability.

关 键 词：CENTROMERE CENP-A cell cycle MITOSIS PHOSPHORYLATION chromosome segregation 

分 类 号：Q343.2[生物学—遗传学]