DNA binding of Xrcc4 protein is associated with V(D)J recombination but not with stimulation of DNA ligase IV activity
DNA binding of Xrcc4 protein is associated with V(D)J recombination but not with stimulation of DNA ligase IV activity
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DOI：
10.1093/emboj/18.7.2008
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发表时间：
1999-04-01
期刊：
影响因子：
11.4
通讯作者：
Gellert, M
中科院分区：
文献类型：
--
作者：
Modesti, M;Hesse, JE;Gellert, M
哺乳动物细胞通过末端连接修复免受DNA双链断裂的影响，缺乏Xrcc4蛋白的细胞对诱导DNA双链断裂的药物过敏，无法完成V(D)J重组。缺乏Xrcc4的细胞对断裂DNA末端的残余修复需要短序列同源性，因此可能与Xrcc4在末端比对中有关。我们发现Xrcc4与DNA结合，并且更喜欢带有缺口或断裂末端的DNA。Xrcc4也与DNA连接酶IV结合并增强其连接活性。这种刺激作用显示在酶的腺苷化过程中发生。Xrcc4的DNA结合与Xrcc4缺陷细胞中V(D)J重组缺陷的互补相关，但不是刺激DNA连接酶IV所必需的。因此，Xrcc4与DNA结合的能力表明其功能独立于DNA连接酶IV。
Mammalian cells are protected from the effects of DNA double-strand breaks by end-joining repair, Cells lacking the Xrcc4 protein are hypersensitive to agents that induce DNA double-strand breaks, and are unable to complete V(D)J recombination, The residual repair of broken DNA ends in XRCC4-deficient cells requires short sequence homologies, thus possibly implicating Xrcc4 in end alignment. We show that Xrcc4 binds DNA, and prefers DNA with nicks or broken ends. Xrcc4 also binds to DNA ligase IV and enhances its joining activity. This stimulatory effect is shown to occur at the adenylation of the enzyme. DNA binding of Xrcc4 is correlated with its complementation of the V(D)J recombination defects in XRCC4-deficient cells, but is not required for stimulation of DNA ligase IV. Thus, the ability of Xrcc4 to bind to DNA suggests functions independent of DNA ligase IV.