| First Author | Hasham MG | Year | 2010 |
| Journal | Nat Immunol | Volume | 11 |
| Issue | 9 | Pages | 820-6 |
| PubMed ID | 20657597 | Mgi Jnum | J:163929 |
| Mgi Id | MGI:4830201 | Doi | 10.1038/ni.1909 |
| Citation | Hasham MG, et al. (2010) Widespread genomic breaks generated by activation-induced cytidine deaminase are prevented by homologous recombination. Nat Immunol 11(9):820-6 |
| abstractText | Activation-induced cytidine deaminase (AID) is required for somatic hypermutation and immunoglobulin class switching in activated B cells. Because AID has no known target-site specificity, there have been efforts to identify non-immunoglobulin AID targets. We show here that AID acts promiscuously, generating widespread DNA double-strand breaks (DSBs), genomic instability and cytotoxicity in B cells with less homologous recombination ability. We demonstrate that the homologous-recombination factor XRCC2 suppressed AID-induced off-target DSBs, promoting B cell survival. Finally, we suggest that aberrations that affect human chromosome 7q36, including XRCC2, correlate with genomic instability in B cell cancers. Our findings demonstrate that AID has promiscuous genomic DSB-inducing activity, identify homologous recombination as a safeguard against off-target AID action, and have implications for genomic instability in B cell cancers. |
