| First Author | Rada C | Year | 2004 |
| Journal | Mol Cell | Volume | 16 |
| Issue | 2 | Pages | 163-71 |
| PubMed ID | 15494304 | Mgi Jnum | J:94542 |
| Mgi Id | MGI:3513244 | Doi | 10.1016/j.molcel.2004.10.011 |
| Citation | Rada C, et al. (2004) Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A/T-focused phase of somatic mutation. Mol Cell 16(2):163-71 |
| abstractText | AID-mediated deamination of dC residues within the immunoglobulin locus generates dU:dG lesions whose resolution leads to class-switch recombination and somatic hypermutation. The dU:dG pair is a mismatch and comprises a base foreign to DNA and is, thus, recognized by proteins from both base excision (uracil-DNA glycosylase, UNG) and mismatch recognition (MSH2/MSH6) pathways. Strikingly, while antibody diversification is perturbed by single deficiency in either UNG or MSH2, combined UNG/MSH2 deficiency leads to a total ablation both of switch recombination and of IgV hypermutation at dA:dT pairs. The initiating dU:dG lesions appear not to be recognized and are simply replicated over. The results indicate that the major pathway for switch recombination occurs through uracil excision with mismatch recognition of dU:dG providing a backup; the second phase of hypermutation (essentially introducing mutations solely at dA:dT pairs) is triggered by mismatch recognition of the dU:dG lesion with uracil excision providing a backup. |
