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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*Note: In the version of this article originally published online, the values for "Total base number" in Table 4 were incomplete. The correct numbers are as follows: 24,487; 25,008; 23,445; 10,420; and 20,840. Line 3 of the legend for Figure 1 should read "mAID, mouse AID," and line 1 of the legend to Table 2 legend should begin "DNA". This error has been corrected for the HTML and print versions of this article.
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We thank J.C. Weill and C.A. Reynaud for providing BL2 cells; S. Fagarasan for critical comments and reading the manuscript; E. Inoue, Y. Sasaki and Y. Hosoe for technical assistance; and Y. Shiraki for preparation of the manuscript. Supported by Ministry of Education, Science, Sports, and Culture of Japan (Center of Excellence Grant).
The authors declare no competing financial interests.
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Apurinic/apyrimidinic endonuclease 1 (APE1) is dispensable for activation-induced cytidine deaminase (AID)-dependent somatic hypermutation in the immunoglobulin gene
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