Subjects: Biology >> Biophysics >> Cell Biology submitted time 2016-05-12
Yu, Zhouliang
Zhou, Xiang
Wang, Wenjing
Deng, Wenqiang
Fang, Junnan
Hu, Hao
Wang, Zichen
Cui, Lei
Shen, Jing
Ou, Guangshuo
Yang, Na
Chen, Ping
Xu, Rui-Ming
Li, Guohong
Yu, Zhouliang
Deng, Wenqiang
Fang, Junnan
Hu, Hao
Peng, Shengyi
Li, Shangze
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/PP1 alpha 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.
Peer Review Status:
Awaiting Review
Subjects: Biology >> Biophysics >> Cell Biology submitted time 2016-05-12
Fang, Junnan
Liu, Yuting
Wei, Yun
Deng, Wenqiang
Yu, Zhouliang
Huang, Li
Teng, Yan
Yao, Ting
You, Qinglong
Ruan, Haihe
Chen, Ping
Xu, Rui-Ming
Li, Guohong
Fang, Junnan
Liu, Yuting
Deng, Wenqiang
Yu, Zhouliang
You, Qinglong
Abstract： Specific recognition of centromere-specific histone variant CENP-A-containing chromatin by CENP-N is an essential process in the assembly of the kinetochore complex at centromeres prior to mammalian cell division. However, the mechanisms of CENP-N recruitment to centromeres/kinetochores remain unknown. Here, we show that a CENP-A-specific RG loop (Arg80/Gly81) plays an essential and dual regulatory role in this process. The RG loop assists the formation of a compact "ladder-like" structure of CENP-A chromatin, concealing the loop and thus impairing its role in recruiting CENP-N. Upon G1/S-phase transition, however, centromeric chromatin switches from the compact to an open state, enabling the now exposed RG loop to recruit CENP-N prior to cell division. Our results provide the first insights into the mechanisms by which the recruitment of CENP-N is regulated by the structural transitions between compaction and relaxation of centromeric chromatin during the cell cycle.
Peer Review Status:Awaiting Review
Hits
Hits
Downloads
Comment