The mammalian INO80 complex is recruited to DNA damage sites in an ARP8 dependent manner
The mammalian INO80 complex is recruited to DNA damage sites in an ARP8 dependent manner
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DOI：
10.1016/j.bbrc.2010.10.066
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发表时间：
2010-11-26
影响因子：
3.1
通讯作者：
Murakami, Yasufumi
中科院分区：
文献类型：
--
作者：
Kashiwaba, Shu-ichiro;Kitahashi, Kazuyuki;Murakami, Yasufumi
染色质结构的动态变化对于有效的DNA加工是必不可少的，如转录复制和DNA修复，组蛋白修饰和依赖于ATP的染色质重塑是染色质结构改变的重要因素。INO80染色质重塑复合体在酵母DNA双链断裂(DSB)的HR介导的修复中起重要作用。INO80复合体通过与磷酸化组蛋白H2A直接相互作用被招募到DSB的位点，促进DSB末端的加工，但哺乳动物INO80复合体在DNA修复中的功能大多尚不清楚。在这里，我们证明了哺乳动物的INO80复合体被招募到激光诱导的DNA损伤部位我们还发现，肌动蛋白相关蛋白ARP8是将哺乳动物INO80复合体招募到DNA损伤部位所必需的一个重要亚基，尽管酵母INO80复合体的招募需要它的Nhp10或Arp4亚基。这些结果表明，哺乳动物INO80复合体也被招募到DNA损伤部位，类似于酵母INO80复合体，但这种招募的机制可能与酵母INO80复合体不同。这些发现为哺乳动物细胞DNA修复的机制提供了新的见解(C)2010 Elsevier Inc.版权所有
Dynamic changes in chromatin structure are essential for efficient DNA processing such as transcription replication and DNA repair Histone modifications and ATP-dependent chromatin remodeling are important for the alteration of chromatin structure The INO80 chromatin remodeling complex plays an important role in HR-mediated repair of DNA double-strand breaks (DSBs) In yeast the INO80 complex is recruited to the sites of DSBs via direct interaction with phosphorylated histone H2A and facilitates the processing of DSB ends However the function of the mammalian INO80 complex in DNA repair is mostly unknown Here we show that the mammalian INO80 complex is recruited to the laser-Induced DNA damage sites in a phosphorylated H2AX (gamma H2AX)-independent manner We also found that an actin-related protein ARP8 is an important subunit that is required for the recruitment of the mammalian INO80 complex to the DNA damage sites although the recruitment of the yeast INO80 complex requires its Nhp10 or Arp4 subunits These results suggest that the mammalian INO80 complex is also recruited to DNA damage sites similarly to the yeast INO80 complex but the mechanism of this recruitment may be different from that of the yeast INO80 complex These findings provide new insights Into the mechanisms of DNA repair in mammalian cells (C) 2010 Elsevier Inc All rights reserved