| First Author | Shen HM | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 8 | Pages | 5386-92 |
| PubMed ID | 17015724 | Mgi Jnum | J:125031 |
| Mgi Id | MGI:3723381 | Doi | 10.4049/jimmunol.177.8.5386 |
| Citation | Shen HM, et al. (2006) Somatic hypermutation and class switch recombination in Msh6(-/-)Ung(-/-) double-knockout mice. J Immunol 177(8):5386-92 |
| abstractText | Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by activation-induced cytosine deaminase (AID). The uracil, and potentially neighboring bases, are processed by error-prone base excision repair and mismatch repair. Deficiencies in Ung, Msh2, or Msh6 affect SHM and CSR. To determine whether Msh2/Msh6 complexes which recognize single-base mismatches and loops were the only mismatch-recognition complexes required for SHM and CSR, we analyzed these processes in Msh6(-/-)Ung(-/-) mice. SHM and CSR were affected in the same degree and fashion as in Msh2(-/-)Ung(-/-) mice; mutations were mostly C,G transitions and CSR was greatly reduced, making Msh2/Msh3 contributions unlikely. Inactivating Ung alone reduced mutations from A and T, suggesting that, depending on the DNA sequence, varying proportions of A,T mutations arise by error-prone long-patch base excision repair. Further, in Msh6(-/-)Ung(-/-) mice the 5' end and the 3' region of Ig genes was spared from mutations as in wild-type mice, confirming that AID does not act in these regions. Finally, because in the absence of both Ung and Msh6, transition mutations from C and G likely are 'footprints' of AID, the data show that the activity of AID is restricted drastically in vivo compared with AID in cell-free assays. |
