The response to and repair of RAG-mediated DNA double-strand breaks.
The response to and repair of RAG-mediated DNA double-strand breaks.
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DOI：
10.1146/annurev-immunol-030409-101320
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发表时间：
2012
影响因子：
29.7
通讯作者：
Sleckman BP
中科院分区：
文献类型：
--
作者：
Helmink BA;Sleckman BP
发育中的淋巴细胞必须组装编码B细胞和T细胞受体的抗原受体基因。该过程通过V（D）J重组反应来执行，其可分为DNA切割和DNA连接步骤。前者是由淋巴细胞特异性RAG核酸内切酶进行的，该核酸内切酶介导两个重组基因片段及其侧翼RAG识别序列处的DNA切割。RAG切割产生四个断裂的DNA末端，其通过形成编码和信号接头的非同源末端连接来修复。在极少数情况下，这些DNA末端可能异常连接，形成染色体病变，如易位、缺失和倒位，可能导致细胞转化和淋巴肿瘤。我们讨论了RAG诱导的DSB激活的DNA损伤反应，重点是促进其正常修复和防止其异常分辨率的组件途径。此外，我们还讨论了这种DNA损伤反应如何影响淋巴细胞发育的重要过程。
Developing lymphocytes must assemble antigen receptor genes encoding the B cell and T cell receptors. This process is executed by the V(D)J recombination reaction, which can be divided into DNA cleavage and DNA joining steps. The former is carried out by a lymphocyte-specific RAG endonuclease, which mediates DNA cleavage at two recombining gene segments and their flanking RAG recognition sequences. RAG cleavage generates four broken DNA ends that are repaired by non-homologous end joining forming coding and signal joints. On rare occasions, these DNA ends may join aberrantly forming chromosomal lesions such as translocations, deletions and inversions that have the potential to cause cellular transformation and lymphoid tumors. We discuss the activation of DNA damage responses by RAG-induced DSBs focusing on the component pathways that promote their normal repair and guard against their aberrant resolution. Moreover, we discuss how this DNA damage response impacts processes important for lymphocyte development.
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影响因子：
56.9
作者：
Celeste, A;Petersen, S;Nussenzweig, A
通讯作者：
Nussenzweig, A
影响因子：
16
作者：
Callen, Elsa;Jankovic, Mila;Wong, Nancy;Zha, Shan;Chen, Hua-Tang;Difilippantonio, Simone;Di Virgilio, Michela;Heidkamp, Gordon;Alt, Frederick W.;Nussenzweig, Andre;Nussenzweig, Michel
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Nussenzweig, Michel
影响因子：
64.5
作者：
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通讯作者：
Alt, FW
影响因子：
10.5
作者：
CHEN, YY;WANG, LC;ROSENBERG, N
通讯作者：
ROSENBERG, N
影响因子：
64.5
作者：
BAER, R;CHEN, KC;RABBITTS, TH
通讯作者：
RABBITTS, TH