AID is required to initiate Nbs1/γ-H2AX focus formation and mutations at sites of class switching
AID is required to initiate Nbs1/γ-H2AX focus formation and mutations at sites of class switching
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DOI：
10.1038/414660a
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发表时间：
2001-12-06
期刊：
影响因子：
64.8
通讯作者：
Nussenzweig, A
中科院分区：
文献类型：
--
作者：
Petersen, S;Casellas, R;Nussenzweig, A
类别转换重组（CSR）是一种区域特异性DNA重组反应，将一个免疫球蛋白重链恒定区（CH）基因替换为另一个。这使得单个可变（V）区基因能够与不同的下游CH基因结合使用，每个下游CH基因具有独特的生物活性。介导CSR的分子机制尚未确定，但该反应需要激活诱导的胞苷脱氨酶（AID），一种假定的RNA编辑酶（1）。在这里，我们报道了奈梅亨断裂综合征蛋白（Nbs 1）和磷酸化H2 A组蛋白家族成员X（gamma -H2 AX，也称为gamma -H2 afx），它们促进DNA双链断裂（DSB）修复（2-4），在经历CSR的细胞中，在细胞周期的G1期在CH区形成核灶，并且在H2 AX（-/-）小鼠中转换受损。在CSR期间，Nbs 1和γ-H2 AX定位于IgH基因座依赖于AID。此外，AID是诱导CSR之前的开关区（S mu）特异性DNA损伤所必需的。这些结果将AID功能置于启动CSR的DNA修饰的上游。
Class switch recombination (CSR) is a region-specific DNA recombination reaction that replaces one immunoglobulin heavy-chain constant region (CH) gene with another. This enables a single variable (V) region gene to be used in conjunction with different downstream CH genes, each having a unique biological activity. The molecular mechanisms that mediate CSR have not been defined, but activation-induced cytidine deaminase (AID), a putative RNA-editing enzyme, is required for this reaction(1). Here we report that the Nijmegen breakage syndrome protein (Nbs1) and phosphorylated H2A histone family member X (gamma -H2AX, also known as gamma -H2afx), which facilitate DNA double-strand break (DSB) repair(2-4), form nuclear foci at the CH region in the G1 phase of the cell cycle in cells undergoing CSR, and that switching is impaired in H2AX(-/-) mice. Localization of Nbs1 and gamma -H2AX to the IgH locus during CSR is dependent on AID. In addition, AID is required for induction of switch region (S mu)-specific DNA lesions that precede CSR. These results place AID function upstream of the DNA modifications that initiate CSR.