INO80 and γ-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair
INO80 and γ-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair
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DOI：
10.1016/j.cell.2004.11.037
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发表时间：
2004-12-17
期刊：
影响因子：
64.5
通讯作者：
Shen, XT
中科院分区：
文献类型：
--
作者：
Morrison, AJ;Highland, J;Shen, XT
虽然atp依赖性染色质重塑在转录中的作用已经确立，但染色质重塑与DNA修复之间的联系仍然难以捉摸。我们发现进化上保守的INO80染色质重塑复合体直接参与酵母双链断裂（DSB）的修复。INO80复合体通过与DNA损伤诱导的磷酸化组蛋白H2A （γ - h2ax）的特异性相互作用被募集到HO内切酶诱导的DSB中。这种相互作用需要Nhp10，它是INO80复合体的一种类似hmg的亚基。Nhp10或γ - h2ax的缺失导致INO80向DSB的募集减少。最后，INO80复合物的组分显示出与RAD52 DNA修复途径（酵母中DSB修复的主要途径）的合成遗传相互作用。我们的发现揭示了atp依赖性染色质重塑在核过程中的新作用，并表明atp依赖性染色质重塑复合体可以读取DNA修复组蛋白代码。
While the role of ATP-dependent chromatin remodeling in transcription is well established, a link between chromatin remodeling and DNA repair has remained elusive. We have found that the evolutionarily conserved INO80 chromatin remodeling complex directly participates in the repair of a double-strand break (DSB) in yeast. The INO80 complex is recruited to a HO endonuclease-induced DSB through a specific interaction with the DNA damage-induced phosphorylated histone H2A (gamma-H2AX). This interaction requires Nhp10, an HMG-like subunit of the INO80 complex. The loss of Nhp10 or gamma-H2AX results in reduced INO80 recruitment to the DSB. Finally, components of the INO80 complex show synthetic genetic interactions with the RAD52 DNA repair pathway, the main pathway for DSB repair in yeast. Our findings reveal a new role of ATP-dependent chromatin remodeling in nuclear processes and suggest that an ATP-dependent chromatin remodeling complex can read a DNA repair histone code.