Reina-San-Martin Bernardo, Chen Hua Tang, Nussenzweig André, Nussenzweig Michel C
Howard Hughes Medical Institute, The Rockefeller University, 1230 York Ave., New York, NY 10021, USA.
J Exp Med. 2004 Nov 1;200(9):1103-10. doi: 10.1084/jem.20041162.
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.
共济失调毛细血管扩张症突变（ATM）激酶对于启动导致细胞周期检查点和DNA双链断裂修复的信号通路至关重要。在缺乏ATM的情况下，人类和小鼠表现出原发性免疫缺陷，包括血清抗体滴度低，但ATM在抗原驱动的免疫球蛋白基因多样化中的作用尚未明确。在这里，我们表明，虽然ATM对于体细胞高频突变是可有可无的，但它是有效类别转换重组（CSR）所必需的。CSR缺陷并非由于转换区转录、可及性、DNA损伤检查点蛋白募集或短程转换区内重组的改变。只有长程转换区间重组存在缺陷，这表明ATM在CSR期间的转换区突触形成中具有意想不到的作用。
