Separate domains of AID are required for somatic hypermutation and class-switch recombination

被引:0
|
作者
Reiko Shinkura
Satomi Ito
Nasim A Begum
Hitoshi Nagaoka
Masamichi Muramatsu
Kazuo Kinoshita
Yoshimasa Sakakibara
Hiroko Hijikata
Tasuku Honjo
机构
[1] Graduate School of Medicine,Department of Medical Chemistry and Molecular Biology
[2] Kyoto University,undefined
[3] Yoshida,undefined
[4] Sakyo-ku,undefined
来源
Nature Immunology | 2004年 / 5卷
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摘要
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 μ 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.
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页码:707 / 712
页数:5
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