CHD4 in the DNA-damage response and cell cycle progression: not so NuRDy now.
CHD4 in the DNA-damage response and cell cycle progression: not so NuRDy now.
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DOI：
10.1042/bst20130027
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发表时间：
2013-06
影响因子：
3.9
通讯作者：
Hendrich B
中科院分区：
文献类型：
--
作者：
O'Shaughnessy A;Hendrich B
CHD 4（chromodomain-helicase-DNA-binding 4）（或Mi-2β）蛋白是NuRD（核小体重塑和脱乙酰化）复合物的基础组分。长期以来，人们就知道NuRD在转录调节中发挥作用，并且在整个动物和植物王国中都是保守的。近年来，越来越多的证据表明，CHD 4既可以在NuRD复合物之外发挥作用，也可以在转录调控以外的细胞过程中发挥重要作用。许多功能丧失研究已经确定了CHD 4在DNA损伤反应和细胞周期进展中的重要作用，通过S期和G2期。此外，作为NuRD的一部分，它参与调节p53的乙酰化水平，从而间接调节G1/S细胞周期检查点。尽管CHD 4与细胞周期的关系有些复杂，但最近的证据表明，CHD 4可能在人类癌症发生中发挥一些肿瘤抑制功能。CHD 4是NuRD复合物的定义成员，但越来越多的证据表明，CHD 4在DNA损伤反应和细胞周期进程以及转录调控中也起着重要的NuRD独立作用。
The CHD4 (chromodomain-helicase-DNA-binding 4) (or Mi-2β) protein is a founding component of the NuRD (nucleosome remodelling and deacetylation) complex. NuRD has long been known to function in transcriptional regulation, and is conserved throughout the animal and plant kingdoms. In recent years, evidence has steadily accumulated indicating that CHD4 can both function outside of the NuRD complex and also play important roles in cellular processes other than transcriptional regulation. A number of loss-of-function studies have identified important roles for CHD4 in the DNA-damage response and in cell cycle progression through S-phase and into G2. Furthermore, as part of NuRD, it participates in regulating acetylation levels of p53, thereby indirectly regulating the G1/S cell cycle checkpoint. Although CHD4 has a somewhat complicated relationship with the cell cycle, recent evidence indicates that CHD4 may exert some tumour-suppressor functions in human carcinogenesis. CHD4 is a defining member of the NuRD complex, but evidence is accumulating that CHD4 also plays important NuRD-independent roles in the DNA-damage response and cell cycle progression, as well as in transcriptional regulation.