Linking double-stranded DNA breaks to the recombination activating gene complex directs repair to the nonhomologous end-joining pathway

Linking double-stranded DNA breaks to the recombination activating gene complex directs repair to the nonhomologous end-joining pathway
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DOI:
10.1073/pnas.0610928104
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发表时间:
2007-10-23
影响因子:
11.1
通讯作者:
Meek, Katheryn
Meek, Katheryn
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cui, Xiaoping;Meek, Katheryn

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两种主要的DNA修复途径,非同源末端连接(NHEJ)和同源重组(HR),在所有真核生物中修复双链DNA断裂(DSB)。此外,已经报道了几种替代的末端连接途径(或子途径),其特征性地在DNA末端使用短序列同源性以促进连接。细胞如何选择使用哪种DNA修复途径(在任何特定的DSB)是一个核心的,在很大程度上没有答案的问题。对于一种类型的DSB,显然没有选择。由淋巴细胞特异性重组激活基因(RAG)核酸内切酶介导的DSB几乎完全由NHEJ修复。在这里,我们证明了非RAG介导的DSB可以通过与RAG核酸内切酶的物理结合类似地被迫进入NHEJ途径。
Two major DNA repair pathways, nonhomologous end-joining (NHEJ) and homologous recombination (HR), repair double- stranded DNA breaks (DSBs) in all eukaryotes. Additionally, several alternative end-joining pathways (or subpathways) have been reported that characteristically use short-sequence homologies at the DNA ends to facilitate joining. How a cell chooses which DNA repair pathway to use (at any particular DSB) is a central and largely unanswered question. For one type of DSB, there is apparently no choice. DSBs mediated by the lymphocyte-specific recombination activating gene (RAG) endonuclease are repaired virtually exclusively by NHEJ. Here we demonstrate that non-RAG-mediated DSBs can be similarly forced into the NHEJ pathway by physical association with the RAG endonuclease.