Condensin recruitment to chromatin is inhibited by Chk2 kinase in response to DNA damage

被引:14
作者
Zhang, Tao [1 ,2 ,3 ]
Si-Hoe, San Ling [1 ]
Hudson, Damien F. [2 ,3 ]
Surana, Uttam [1 ,4 ,5 ]
机构
[1] Agcy Sci Technol & Res, Inst Mol & Cell Biol, Singapore, Singapore
[2] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia
[3] Univ Melbourne, Royal Childrens Hosp, Dept Pediat, Melbourne, Vic, Australia
[4] Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore
[5] Agcy Sci Technol & Res, Bioproc Technol Inst, Singapore, Singapore
基金
澳大利亚国家健康与医学研究理事会;
关键词
Cell Cycle; Checkpoint; Chromosome condensation; DNA damage; Mitosis; MITOTIC CHROMOSOME CONDENSATION; CHECKPOINT; PHOSPHORYLATION; ASSOCIATION; DISRUPTION; ACTIVATION; DISTINCT; HOMOLOG; PATHWAY; COMPLEX;
D O I
10.1080/15384101.2016.1249075
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The DNA damage checkpoint, when activated in response to genotoxic damage during S phase, arrests cells in G2 phase of the cell cycle. ATM, ATR, Chk1 and Chk2 kinases are the main effectors of this checkpoint pathway. The checkpoint kinases prevent the onset of mitosis by eliciting well characterized inhibitory phosphorylation of Cdk1. Since Cdk1 is required for the recruitment of condensin, it is thought that upon DNA damage the checkpoint also indirectly blocks chromosome condensation via Cdk1 inhibition. Here we report that the G2 damage checkpoint prevents stable recruitment of the chromosome-packaging-machinery components condensin complex I and II onto the chromatin even in the presence of an active Cdk1. DNA damage-induced inhibition of condensin subunit recruitment is mediated specifically by the Chk2 kinase, implying that the condensin complexes are targeted by the checkpoint in response to DNA damage, independently of Cdk1 inactivation. Thus, the G2 checkpoint directly prevents stable recruitment of condensin complexes to actively prevent chromosome compaction during G2 arrest, presumably to ensure efficient repair of the genomic damage.
引用
收藏
页码:3454 / 3470
页数:17
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