Response to RAG-mediated V(D)J cleavage by NBS1 and γ-H2AX
Response to RAG-mediated V(D)J cleavage by NBS1 and γ-H2AX
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DOI：
10.1126/science.290.5498.1962
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发表时间：
2000-12-08
期刊：
影响因子：
56.9
通讯作者：
Nussenzweig, A
中科院分区：
文献类型：
--
作者：
Chen, HT;Bhandoola, A;Nussenzweig, A
影响细胞对DNA损伤反应的遗传性疾病的特征是涉及抗原受体基因座的高易位率和对淋巴恶性肿瘤的易感性增加。我们报道了与辐射诱导的DNA双链断裂（DSB）相关的奈梅亨断裂综合征蛋白（NBS 1）和组蛋白γ-H2 AX也在V（D）J（可变、多样、连接）重组诱导的DSB位点被发现。在发育中的胸腺细胞中，NBS 1和gamma -H2 AX形成核灶，与T细胞受体α基因座共定位，以响应重组激活基因（RAG）蛋白介导的V（D）J切割。我们的研究结果表明，通过NBS 1和γ-H2 AX对T细胞受体重组中间体的监视对于预防致癌易位可能是重要的。
Genetic disorders affecting cellular responses to DNA damage are characterized by high rates of translocations involving antigen receptor loci and increased susceptibility to lymphoid malignancies. We report that the Nijmegen breakage syndrome protein (NBS1) and histone gamma -H2AX, which associate with irradiation-induced DNA double-strand breaks (DSBs), are also found at sites of V(D)J (variable, diversity, joining) recombination-induced DSBs. In developing thymocytes, NBS1 and gamma -H2AX form nuclear foci that colocalize with the T cell receptor alpha locus in response to recombination activating gene (RAG) protein-mediated V(D)J cleavage. Our results suggest that surveillance of T cell receptor recombination intermediates by NBS1 and gamma -H2AX may be important for preventing oncogenic translocations.