Separate domains of AID are required for somatic hypermutation and class-switch recombination
Separate domains of AID are required for somatic hypermutation and class-switch recombination
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DOI：
10.1038/ni1086
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发表时间：
2004-07-01
影响因子：
30.5
通讯作者：
Honjo, T
中科院分区：
文献类型：
--
作者：
Shinkura, R;Ito, S;Honjo, T
激活诱导的胞苷脱氨酶（AID）是类转换重组（CSR）和体细胞超突变（SHM）所必需的。在AID的C-末端区域具有变化的突变体保留SHM，但失去CSR活性。在这里，我们描述了5个突变体的N-末端区域的AID，造成选择性缺陷SHM，但保留CSR，这表明CSR和SHM活动的AID可能会通过相互作用的CSR或SHM特定的辅因子与不同的域的AID解离。与表达C-末端AID突变体的细胞不同，表达N-末端AID突变体的B细胞在开关mu区域中具有突变，表明此类突变是由参与CSR而不是SHM的反应产生的。因此，我们建议，单独的域的艾滋病相互作用的特定辅因子，以调节这两个不同的基因事件在一个目标特定的方式。
Activation-induced cytidine deaminase (AID) is essential for class-switch recombination (CSR) and somatic hypermutation (SHM). Mutants with changes in the C-terminal region of AID retain SHM but lose CSR activity. Here we describe five mutants with alterations in the N-terminal region of AID that caused selective deficiency in SHM but retained CSR, suggesting that the CSR and SHM activities of AID may dissociate via interaction of CSR- or SHM-specific cofactors with different domains of AID. Unlike cells expressing C-terminal AID mutants, B cells expressing N-terminal AID mutants had mutations in the switch mu region, indicating that such mutations are generated by reactions involved in CSR but not SHM. Thus, we propose that separate domains of AID interact with specific cofactors to regulate these two distinct genetic events in a target-specific way.