C-terminal region of DNA ligase IV drives XRCC4/DNA ligase IV complex to chromatin
C-terminal region of DNA ligase IV drives XRCC4/DNA ligase IV complex to chromatin
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DOI：
10.1016/j.bbrc.2013.08.068
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发表时间：
2013-09-20
影响因子：
3.1
通讯作者：
Matsumoto, Yoshihisa
中科院分区：
文献类型：
--
作者：
Liu, Sicheng;Liu, Xunyue;Matsumoto, Yoshihisa
DNA连接酶IV（LIG 4）和XRCC 4形成复合物以在DNA双链断裂（DSB）修复的最后步骤通过非同源末端连接（NHEJ）连接两个DNA末端。目前还不完全清楚这些蛋白质是如何被招募到DSB的。最近，我们证明了辐射诱导的染色质结合XRCC 4的生化分馏使用去污剂Nonidet P-40。在本研究中，我们研究了LIG 4在XRCC 4/LIG 4复合物向染色质募集中的作用。XRCC 4的染色质结合依赖于LIG 4的存在。LIG 4的两个BRCT结构域（分别为W725 R和W893 R）中的突变降低了LIG 4和XRCC 4的染色质结合。LIG 4的C-末端片段（LIG 4-CT）不含N-末端催化结构域，可与染色质结合。具有W725 R或W893 R突变的LIG 4-CT可以与染色质结合，但不能支持XRCC 4的染色质结合。LIG 4的C-末端区域与染色质相互作用的能力可能为我们提供了通过NHEJ修复DSB的机制。(C)2013 Elsevier Inc. All rights reserved.
DNA ligase IV (LIG4) and XRCC4 form a complex to ligate two DNA ends at the final step of DNA double-strand break (DSB) repair through non-homologous end-joining (NHEJ). It is not fully understood how these proteins are recruited to DSBs. We recently demonstrated radiation-induced chromatin binding of XRCC4 by biochemical fractionation using detergent Nonidet P-40. In the present study, we examined the role of LIG4 in the recruitment of XRCC4/LIG4 complex to chromatin. The chromatin binding of XRCC4 was dependent on the presence of LIG4. The mutations in two BRCT domains (W725R and W893R, respectively) of LIG4 reduced the chromatin binding of LIG4 and XRCC4. The C-terminal fragment of LIG4 (LIG4-CT) without N-terminal catalytic domains could bind to chromatin with XRCC4. LIG4-CT with W725R or W893R mutation could bind to chromatin but could not support the chromatin binding of XRCC4. The ability of C-terminal region of LIG4 to interact with chromatin might provide us with an insight into the mechanisms of DSB repair through NHEJ. (C) 2013 Elsevier Inc. All rights reserved.