Separate domains of AID are required for somatic hypermutation and class-switch recombination.
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 micro 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.
Shinkura
Reiko
R
Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
Ito
Satomi
S
Begum
Nasim A
NA
Nagaoka
Hitoshi
H
Muramatsu
Masamichi
M
Kinoshita
Kazuo
K
Sakakibara
Yoshimasa
Y
Hijikata
Hiroko
H
Honjo
Tasuku
T
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D041681:NIH 3T3 Cells; D019913:Nuclear Localization Signals / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics* / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D019913:Nuclear Localization Signals; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase