Regulation of chromatin architecture by the PWWP domain-containing DNA damage-responsive factor EXPAND1/MUM1.

Regulation of chromatin architecture by the PWWP domain-containing DNA damage-responsive factor EXPAND1/MUM1.
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DOI:
10.1016/j.molcel.2009.12.040
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发表时间:
2010-03-26
期刊:
影响因子:
16
通讯作者:
Chen, Junjie
Chen, Junjie
中科院分区:
生物学1区
文献类型:
--
作者:
Huen, Michael S. Y.;Huang, Jun;Leung, Justin W. C.;Sy, Shirley M. -H.;Leung, Ka Man;Ching, Yick-Pang;Tsao, Sai Wah;Chen, Junjie

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染色质结构的动态变化促进了多种生物学事件,包括DNA复制、修复、重组和基因转录。最近的证据表明,DNA损伤导致染色质改变,以促进适当的检查点激活和DNA修复。在这里,我们报告的PWWP结构域的蛋白EXPAND1作为染色质,在响应DNA损伤,作为一个辅助因子,以促进细胞存活的建筑组件的鉴定。EXPAND1的缺失或其PWWP结构域的失活导致染色质致密化。在DNA损伤后,EXPAND1通过与53BP1的直接相互作用迅速集中在DNA损伤位点附近。这种相互作用的消除损害了损伤诱导的染色质去凝聚,这是伴随着持续的DNA损伤和对遗传毒性应激的超敏反应。总的来说,我们的研究揭示了一个染色质结合因子,它在耦合损伤信号与响应DNA损伤的染色质变化中起辅助作用。
Dynamic changes of chromatin structure facilitate diverse biological events, including DNA replication, repair, recombination, and gene transcription. Recent evidence revealed that DNA damage elicits alterations to the chromatin to facilitate proper checkpoint activation and DNA repair. Here we report the identification of the PWWP domain-containing protein EXPAND1 as an architectural component of the chromatin, which in response to DNA damage, serves as an accessory factor to promote cell survival. Depletion of EXPAND1 or inactivation of its PWWP domain resulted in chromatin compaction. Upon DNA damage, EXPAND1 rapidly concentrates at the vicinity of DNA damage sites via its direct interaction with 53BP1. Ablation of this interaction impaired damage-induced chromatin decondensation, which is accompanied by sustained DNA damage and hypersensitivity to genotoxic stress. Collectively, our study uncovers a chromatin bound factor that serves an accessory role in coupling damage signaling with chromatin changes in response to DNA damage.
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