Histone H2A.Z controls a critical chromatin remodeling step required for DNA double-strand break repair.

Histone H2A.Z controls a critical chromatin remodeling step required for DNA double-strand break repair.
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DOI:
10.1016/j.molcel.2012.09.026
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发表时间:
2012-12-14
期刊:
影响因子:
16
通讯作者:
Price, Brendan D.
Price, Brendan D.
中科院分区:
生物学1区
文献类型:
--
作者:
Xu, Ye;Ayrapetov, Marina K.;Xu, Chang;Gursoy-Yuzugullu, Ozge;Hu, Yiduo;Price, Brendan D.

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DNA 双链断裂 (DSB) 修复期间需要染色质重塑,以促进 DSB 的接近和修复。这种重塑需要组蛋白乙酰化的增加和核小体组织的转变,以创建开放、松弛的染色质结构域。然而,驱动 DSB 核小体结构变化的潜在机制尚不清楚。在这里,我们证明组蛋白 H2A.Z 通过 p400 重塑 ATP 酶交换到 DSB 处的核小体上。 DSB 处的 H2A.Z 交换将染色质转变为开放构象,并且是组蛋白乙酰化和泛素化以及 brca1 复合物加载所必需的。 H2A.Z 交换还限制核酸酶产生单链 DNA,并且是加载 Ku70/80 DSB 修复蛋白所必需的。因此,H2A.Z 交换促进了组蛋白修饰的特定模式和染色质结构的重组,从而导致染色质模板的组装,该模板是 DSB 修复机制的有效底物。
Chromatin remodeling during DNA double-strand break (DSB) repair is required to facilitate access to and repair of DSBs. This remodeling requires increased acetylation of histones and a shift in nucleosome organization to create open, relaxed chromatin domains. However, the underlying mechanism driving changes in nucleosome structure at DSBs is poorly defined. Here, we demonstrate that histone H2A.Z is exchanged onto nucleosomes at DSBs by the p400 remodeling ATPase. H2A.Z exchange at DSBs shifts the chromatin to an open conformation, and is required for acetylation and ubiquitination of histones and for loading of the brca1 complex. H2A.Z exchange also restricts single-stranded DNA production by nucleases and is required for loading of the Ku70/80 DSB repair protein. H2A.Z exchange therefore promotes specific patterns of histone modification and reorganization of the chromatin architecture, leading to the assembly of a chromatin template which is an efficient substrate for the DSB repair machinery.
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