53BP1 links DNA damage-response pathways to immunoglobulin heavy chain class-switch recombination
53BP1 links DNA damage-response pathways to immunoglobulin heavy chain class-switch recombination
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DOI：
10.1038/ni1067
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发表时间：
2004-05-01
影响因子：
30.5
通讯作者：
Carpenter, PB
中科院分区：
文献类型：
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作者：
Manis, JP;Morales, JC;Carpenter, PB
哺乳动物蛋白53BP1在许多细胞类型中会因基因毒性应激（包括DNA双链断裂，DSBs）而被激活。我们现在研究53BP1在B淋巴细胞中发生的特定基因组改变中的潜在功能。尽管53BP1对于V(D)J重组和体细胞高频突变（SHM）（即免疫球蛋白（Ig）可变区外显子组装和突变的过程）是可有可无的，但它对于IgH类别转换重组（CSR）（即IgH恒定区基因交换的重组和缺失过程）是必需的。当受到刺激进行CSR时，53BP1缺陷细胞在C - H种系转录或AID表达方面没有缺陷，然而这些细胞在转换连接方面却大幅减少。目前的研究结果，结合已知的53BP1功能及其激活方式，表明在类别转换重组的连接阶段存在对DSBs的DNA损伤应答。
The mammalian protein 53BP1 is activated in many cell types in response to genotoxic stress, including DNA double-strand breaks (DSBs). We now examine potential functions for 53BP1 in the specific genomic alterations that occur in B lymphocytes. Although 53BP1 was dispensable for V(D)J recombination and somatic hypermutation (SHM), the processes by which immunoglobulin (lg) variable region exons are assembled and mutated, it was required for lgh class-switch recombination (CSR), the recombination and deletion process by which lgh constant region genes are exchanged. When stimulated to undergo CSR, 53BP1-deficient cells exhibited no defect in C-H germline transcription or AID expression, however these cells had a profound decrease in switch junctions. The current findings, in combination with the known 53BP1 functions and how it is activated, implicate the DNA damage response to DSBs in the joining phase of class-switch recombination.