C-terminal deletion of AID uncouples class switch recombination from somatic hypermutation and gene conversion
C-terminal deletion of AID uncouples class switch recombination from somatic hypermutation and gene conversion
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DOI：
10.1016/s1097-2765(03)00309-5
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发表时间：
2003-08-01
期刊：
影响因子：
16
通讯作者：
Nussenzweig, MC
中科院分区：
文献类型：
--
作者：
Barreto, V;Reina-San-Martin, B;Nussenzweig, MC
类别转换重组（CSR）、体细胞超突变（SHM）和抗体基因转换是不同的DNA修饰反应，但都是由激活诱导的胞苷脱氨酶（AID）启动的，AID是一种使单链DNA中的胞苷残基脱氨基的酶。在这里，我们描述了一种突变形式的艾滋病，催化SHM和基因转换，但不CSR。当在E.在大肠杆菌中，AID（Delta 189 -198）比野生型AID更具有催化胞苷脱氨的活性。AID（Delta 189 -198）在真核细胞中表达时也促进高水平的基因转化和SHM，但不能诱导CSR。这些结果强调了C-末端结构域的AID在CSR中的重要作用，这是独立于其胞苷脱氨酶活性，并且不是基因转换或SHM所必需的。
Class-switch recombination (CSR), somatic hypermutation (SHM), and antibody gene conversion are distinct DNA modification reactions, but all are initiated by activation-induced cytidine deaminase (AID), an enzyme that deaminates cytidine residues in single-stranded DNA. Here we describe a mutant form of AID that catalyzes SHM and gene conversion but not CSR. When expressed in E. coli, AID(Delta189-198) is more active in catalyzing cytidine deamination than wild-type AID. AID(Delta189-198) also promotes high levels of gene conversion and SHM when expressed in eukaryotic cells, but fails to induce CSR. These results underscore an essential role for the C-terminal domain of AID in CSR that is independent of its cytidine deaminase activity and that is not required for either gene conversion or SHM.