53BP1 regulates DNA resection and the choice between classical and alternative end joining during class switch recombination.
53BP1 regulates DNA resection and the choice between classical and alternative end joining during class switch recombination.
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DOI：
10.1084/jem.20100244
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发表时间：
2010-04-12
期刊：
影响因子：
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通讯作者：
Nussenzweig MC
中科院分区：
文献类型：
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作者：
Bothmer A;Robbiani DF;Feldhahn N;Gazumyan A;Nussenzweig A;Nussenzweig MC
类别转换重组（CSR）通过连接间隔60-200 kbp的高度重复的DNA元件来使抗体多样化。CSR是由激活诱导的胞苷脱氨酶启动的，胞苷脱氨酶是一种在开关区域产生多个DNA双链断裂（DSB）的酶。开关区域通过需要完整DNA损伤反应和经典或替代非同源末端连接（A-NHEJ）的机制连接。在DNA损伤反应因子中，53 BP 1对CSR的影响最为深远。我们探索的作用，53 BP 1在染色体内DNA修复使用I-SceI引入配对的DSB的IgH基因座。我们发现，53 BP 1的缺失导致共济失调毛细血管扩张症突变依赖性增加的DNA末端切除和切除的DNA优先修复微同源介导的A-NHEJ。我们提出，53 BP 1有利于长距离CSR的部分保护DNA末端的切除，防止A-NHEJ依赖性的短距离重新连接内开关区域DSB。
Class switch recombination (CSR) diversifies antibodies by joining highly repetitive DNA elements, which are separated by 60–200 kbp. CSR is initiated by activation-induced cytidine deaminase, an enzyme that produces multiple DNA double-strand breaks (DSBs) in switch regions. Switch regions are joined by a mechanism that requires an intact DNA damage response and classical or alternative nonhomologous end joining (A-NHEJ). Among the DNA damage response factors, 53BP1 has the most profound effect on CSR. We explore the role of 53BP1 in intrachromosomal DNA repair using I-SceI to introduce paired DSBs in the IgH locus. We find that the absence of 53BP1 results in an ataxia telangiectasia mutated–dependent increase in DNA end resection and that resected DNA is preferentially repaired by microhomology-mediated A-NHEJ. We propose that 53BP1 favors long-range CSR in part by protecting DNA ends against resection, which prevents A-NHEJ–dependent short-range rejoining of intra–switch region DSBs.
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DOI：
10.1073/pnas.0915067107
发表时间：
2010-02-16
影响因子：
11.1
作者：
Boboila, Cristian;Jankovic, Mila;Alt, Frederick W.
通讯作者：
Alt, Frederick W.
影响因子：
21.3
作者：
Jazayeri, A;Falck, J;Jackson, SP
通讯作者：
Jackson, SP
影响因子：
15.3
作者：
Cuadrado, M;Martinez-Pastor, B;Fernandez-Capetillo, O
通讯作者：
Fernandez-Capetillo, O
人CTIP介导DNA终端切除和双链断裂修复的细胞周期控制。
DOI：
10.1074/jbc.m808906200
发表时间：
2009-04-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huertas P;Jackson SP
通讯作者：
Jackson SP
影响因子：
16.8
作者：
通讯作者：
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