| First Author | Zan H | Year | 2005 |
| Journal | EMBO J | Volume | 24 |
| Issue | 21 | Pages | 3757-69 |
| PubMed ID | 16222339 | Mgi Jnum | J:103365 |
| Mgi Id | MGI:3609287 | Doi | 10.1038/sj.emboj.7600833 |
| Citation | Zan H, et al. (2005) The translesion DNA polymerase theta plays a dominant role in immunoglobulin gene somatic hypermutation. EMBO J 24(21):3757-69 |
| abstractText | Immunoglobulin (Ig) somatic hypermutation (SHM) critically underlies the generation of high-affinity antibodies. Mutations can be introduced by error-prone polymerases such as polymerase zeta (Rev3), a mispair extender, and polymerase eta, a mispair inserter with a preference for dA/dT, while repairing DNA lesions initiated by AID-mediated deamination of dC to yield dU:dG mismatches. The partial impairment of SHM observed in the absence of these polymerases led us to hypothesize a main role for another translesion DNA polymerase. Here, we show that deletion in C57BL/6J mice of the translesion polymerase theta, which possesses a dual nucleotide mispair inserter-extender function, results in greater than 60% decrease of mutations in antigen-selected V186.2DJ(H) transcripts and greater than 80% decrease in mutations in the Ig H chain intronic J(H)4-iEmu sequence, together with significant alterations in the spectrum of the residual mutations. Thus, polymerase theta plays a dominant role in SHM, possibly by introducing mismatches while bypassing abasic sites generated by UDG-mediated deglycosylation of AID-effected dU, by extending DNA past such abasic sites and by synthesizing DNA during dU:dG mismatch repair. |
