ATM is required for efficient recombination between immunoglobulin switch regions.

ATM is required for efficient recombination between immunoglobulin switch regions.
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DOI:
10.1084/jem.20041162
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发表时间:
2004-11-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Nussenzweig MC
Nussenzweig MC
中科院分区:
其他
文献类型:
--
作者:
Reina-San-Martin B;Chen HT;Nussenzweig A;Nussenzweig MC

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共济失调毛细血管扩张突变(ATM)激酶在启动导致细胞周期检查点和DNA双链断裂修复的信号通路中起着至关重要的作用。在缺乏ATM的情况下,人类和小鼠表现出包括血清抗体效价低在内的原发免疫缺陷,但ATM在抗原驱动的免疫球蛋白基因多样化中的作用尚未确定。在这里,我们表明,虽然ATM对于体细胞的超突变是必不可少的,但它是有效的类开关重组(CSR)所必需的。CSR的缺陷不是由于开关区转录、可及性、DNA损伤检查点蛋白募集或短程开关内区域重组的改变所致。只有长距离的开关间重组是有缺陷的,这表明在CSR过程中ATM在开关区域突触中扮演了意想不到的角色。
Ataxia telangiectasia mutated (ATM) kinase is critical for initiating the signaling pathways that lead to cell cycle checkpoints and DNA double strand break repair. In the absence of ATM, humans and mice show a primary immunodeficiency that includes low serum antibody titers, but the role of ATM in antigen-driven immunoglobulin gene diversification has not been defined. Here, we show that although ATM is dispensable for somatic hypermutation, it is required for efficient class switch recombination (CSR). The defect in CSR is not due to alterations in switch region transcription, accessibility, DNA damage checkpoint protein recruitment, or short-range intra-switch region recombination. Only long-range inter-switch recombination is defective, indicating an unexpected role for ATM in switch region synapsis during CSR.
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