Chromatin perturbations during the DNA damage response in higher eukaryotes
Chromatin perturbations during the DNA damage response in higher eukaryotes
复制标题
DOI：
10.1016/j.dnarep.2015.09.002
复制
发表时间：
2015-12-01
期刊：
影响因子：
3.8
通讯作者：
Kastan, Michael B.
中科院分区：
文献类型：
--
作者：
Bakkenist, Christopher J.;Kastan, Michael B.
DNA损伤反应是一个广泛使用的术语，包括在DNA损伤和受损复制叉处启动的所有信号传导，因为它延伸到协调DNA修复、细胞周期检查点、细胞死亡和衰老。ATM是一种顶端DNA损伤信号激酶，在DNA双链断裂（DSB）后几乎立即被激活。在DNA修复中具有催化作用的MRE 11-RAD 50-NBS 1（MRN）复合物和KAT 5（Tip 60）乙酰转移酶是暴露于低剂量电离辐射的细胞中最大ATM激酶激活所必需的。DNA损伤的感知发生在高度复杂和异质的染色质环境中。DSB处的染色质去浓缩和组蛋白驱逐可能允许KAT 5结合H3 K9 me 3和H3 K36 me 3、ATM激酶乙酰化和活化。此外，染色质扰动可能是大多数DNA修复的先决条件。DNA修复过程中的核小体解体最早由Smerdon及其同事在20世纪70年代报道，当时在人类细胞中UV诱导的DNA损伤的核苷酸切除修复过程中注意到核小体重排。最近，多功能蛋白核仁素被确定为相关的组蛋白伴侣所需的部分核小体破坏在DBS，招聘的修复酶和DNA修复。值得注意的是，ATM激酶被染色质扰动激活，染色质扰动由各种不直接引起DSB的治疗诱导，包括用组蛋白脱乙酰酶抑制剂治疗。激活ATR的机制的核心，第二个顶端DNA损伤信号激酶，在S期停滞和崩溃的复制叉之外，是染色质解凝聚和组蛋白驱逐与DSB处的DNA末端切除相关。因此，压力是共同的ATM和ATR激酶激活是染色质扰动，我们认为，染色质扰动是足够的，需要诱导的DNA损伤反应。(c)2015爱思唯尔B. V.保留所有权利。
The DNA damage response is a widely used term that encompasses all signaling initiated at DNA lesions and damaged replication forks as it extends to orchestrate DNA repair, cell cycle checkpoints, cell death and senescence. ATM, an apical DNA damage signaling kinase, is virtually instantaneously activated following the introduction of DNA double-strand breaks (DSBs). The MRE11-RAD50-NBS1 (MRN) complex, which has a catalytic role in DNA repair, and the KAT5 (Tip60) acetyltransferase are required for maximal ATM kinase activation in cells exposed to low doses of ionizing radiation. The sensing of DNA lesions occurs within a highly complex and heterogeneous chromatin environment. Chromatin decondensation and histone eviction at DSBs may be permissive for KAT5 binding to H3K9me3 and H3K36me3, ATM kinase acetylation and activation. Furthermore, chromatin perturbation may be a prerequisite for most DNA repair. Nucleosome disassembly during DNA repair was first reported in the 1970s by Smerdon and colleagues when nucleosome rearrangement was noted during the process of nucleotide excision repair of UV-induced DNA damage in human cells. Recently, the multi-functional protein nucleolin was identified as the relevant histone chaperone required for partial nucleosome disruption at DBSs, the recruitment of repair enzymes and for DNA repair. Notably, ATM kinase is activated by chromatin perturbations induced by a variety of treatments that do not directly cause DSBs, including treatment with histone deacetylase inhibitors. Central to the mechanisms that activate ATR, the second apical DNA damage signaling kinase, outside of a stalled and collapsed replication fork in S-phase, is chromatin decondensation and histone eviction associated with DNA end resection at DSBs. Thus, a stress that is common to both ATM and ATR kinase activation is chromatin perturbations, and we argue that chromatin perturbations are both sufficient and required for induction of the DNA damage response. (c) 2015 Elsevier B.V. All rights reserved.