Chromatin modification and NBS1: their relationship in DNA double-strand break repair
Chromatin modification and NBS1: their relationship in DNA double-strand break repair
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DOI：
10.1266/ggs.15-00010
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发表时间：
2015-08-01
影响因子：
1.1
通讯作者：
Kobayashi, Junya
中科院分区：
文献类型：
--
作者：
Saito, Yuichiro;Zhou, Hui;Kobayashi, Junya
染色质修饰（包括组蛋白修饰和染色质重塑）对于DNA双链断裂（DSB）修复以及转录和复制的重要性已得到阐明。H2 AX磷酸化为γ-H2 AX是DSB检测后的第一反应之一，并且这种组蛋白修饰通过触发几个事件（包括DNA损伤反应相关蛋白的积累和随后的同源重组（HR）修复）对DSB损伤反应很重要。其他组蛋白修饰如乙酰化、甲基化和泛素化的作用最近也得到了澄清，特别是在HR修复的背景下。NBS 1是一种多功能蛋白，参与各种DNA损伤反应。其最近鉴定的结合伴侣RNF 20是一种E3泛素连接酶，其促进组蛋白H2 B的单泛素化，这是一个将染色质重塑剂SNF 2 h募集到DSB损伤位点的关键过程。有证据表明SNF 2 h在HR修复中起作用，可能是通过调节末端切除。此外，最近的一些报道表明，SNF 2 h可以在HR修复途径中作为组蛋白重塑剂发挥作用，并且其他已知的组蛋白重塑剂也可以参与DSB损伤反应。另一方面，关于这种染色质修饰和NBS 1在DSB的非同源末端连接（NHEJ）修复和停滞的叉相关损伤反应中的作用的信息非常有限;因此，这些方面和过程需要进一步研究，以促进我们对相关机制和分子参与者的理解。
The importance of chromatin modification, including histone modification and chromatin remodeling, for DNA double-strand break (DSB) repair, as well as transcription and replication, has been elucidated. Phosphorylation of H2AX to gamma-H2AX is one of the first responses following DSB detection, and this histone modification is important for the DSB damage response by triggering several events, including the accumulation of DNA damage response-related proteins and subsequent homologous recombination (HR) repair. The roles of other histone modifications such as acetylation, methylation and ubiquitination have also been recently clarified, particularly in the context of HR repair. NBS1 is a multifunctional protein that is involved in various DNA damage responses. Its recently identified binding partner RNF20 is an E3 ubiquitin ligase that facilitates the monoubiquitination of histone H2B, a process that is crucial for recruitment of the chromatin remodeler SNF2h to DSB damage sites. Evidence suggests that SNF2h functions in HR repair, probably through regulation of end-resection. Moreover, several recent reports have indicated that SNF2h can function in HR repair pathways as a histone remodeler and that other known histone remodelers can also participate in DSB damage responses. On the other hand, information about the roles of such chromatin modifications and NBS1 in non-homologous end joining (NHEJ) repair of DSBs and stalled fork-related damage responses is very limited; therefore, these aspects and processes need to be further studied to advance our understanding of the mechanisms and molecular players involved.