| First Author | Wu X | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 2 | Pages | 934-41 |
| PubMed ID | 15634916 | Mgi Jnum | J:95833 |
| Mgi Id | MGI:3527381 | Doi | 10.4049/jimmunol.174.2.934 |
| Citation | Wu X, et al. (2005) The double-edged sword of activation-induced cytidine deaminase. J Immunol 174(2):934-41 |
| abstractText | Activation-induced cytidine deaminase (AID) is required for Ig class switch recombination, a process that introduces DNA double-strand breaks in B cells. We show in this study that AID associates with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) promoting cell survival, presumably by resolving DNA double-strand breaks. Wild-type cells expressing AID mutants that fail to associate with DNA-PKcs or cells deficient in DNA-PKcs or 53BP1 expressing wild-type AID accumulate gammaH2AX foci, indicative of heightened DNA damage response. Thus, AID has two independent functions. AID catalyzes cytidine deamination that originates DNA double-strand breaks needed for recombination, and it promotes DNA damage response and cell survival. Our results thus resolve the paradox of how B cells undergoing DNA cytidine deamination and recombination exhibit heightened survival and suggest a mechanism for hyperIgM type II syndrome associated with AID mutants deficient in DNA-PKcs binding. |
