Binding of AID to DNA does not correlate with mutator activity.
Binding of AID to DNA does not correlate with mutator activity.
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DOI：
10.4049/jimmunol.1400433
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发表时间：
2014-07-01
期刊：
影响因子：
--
通讯作者：
Chaudhuri J
中科院分区：
文献类型：
--
作者：
Matthews AJ;Husain S;Chaudhuri J
DNA 脱氨酶 AID 通过将可变区 (V) 基因和开关 (S) 区的胞苷脱氨为尿苷来启动体细胞超突变 (SHM) 和类别转换重组 (CSR)。 AID 被招募到 V 基因和 S 区 DNA 的机制尚不清楚。在这里，我们利用 CH12 B 淋巴瘤系来证明，虽然 S 区可以有效地募集 AID 并进行突变和缺失，但 AID 既不结合也不使 V 基因发生突变，从而清楚地证明了免疫球蛋白内基因座的特异性。先前显示RNA结合蛋白Ptpb2的耗尽可以促进AID向S区的募集，使得AID与V基因稳定结合。令人惊讶的是，AID 与 V 基因的结合不会诱导 SHM。这些结果揭示了 AID 结合与其突变活性之间明显缺乏相关性，为 AID 结合下游影响 SHM 所需因素的存在提供了证据。此外，我们的研究结果表明，S 区域是 AID 的首选靶点，并且在 Ptbp2 的帮助下，充当“汇”来隔离其他基因组区域的 AID 活性。
The DNA deaminase AID initiates somatic hypermutation (SHM) and class switch recombination (CSR) by deaminating cytidines to uridines at variable region (V) genes and switch (S) regions. The mechanism by which AID is recruited to V genes and S region DNA is poorly understood. Here we have employed the CH12 B lymphoma line to demonstrate that while S regions can efficiently recruit AID and undergo mutations and deletions, AID neither binds to nor mutates the V gene, thus clearly demonstrating intra-immunoglobulin locus specificity. Depletion of the RNA-binding protein Ptpb2, previously shown to promote recruitment of AID to S regions, enables stable association of AID with the V gene. Surprisingly, AID binding to the V gene does not induce SHM. These results unmask a striking lack of correlation between AID binding and its mutator activity, providing evidence for the presence of factors required downstream of AID binding to effect SHM. Furthermore, our findings suggest that S regions are preferred targets for AID and, aided by Ptbp2, act as “sinks” to sequester AID activity from other genomic regions.
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影响因子：
--
作者：
Matthews, Allysia J.;Zheng, Simin;DiMenna, Lauren J.;Chaudhuri, Jayanta
通讯作者：
Chaudhuri, Jayanta
DOI：
10.1073/pnas.0509969103
发表时间：
2006-01-10
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
32.4
作者：
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通讯作者：
Storb, U
影响因子：
64.8
作者：
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通讯作者：
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