Does DNA repair occur during somatic hypermutation?

Activation-induced deaminase (AID) initiates a flood of DNA damage in the immunoglobulin loci, leading to abasic sites, single-strand breaks and mismatches. It is compelling that some proteins in the canonical base excision and mismatch repair pathways have been hijacked to increase mutagenesis during somatic hypermutation. Thus, the AID-induced mutagenic pathways involve a mix of DNA repair proteins and low fidelity DNA polymerases to create antibody diversity. In this review, we analyze the roles of base excision repair, mismatch repair, and mutagenesis during somatic hypermutation of rearranged variable genes. The emerging view is that faithful base excision repair occurs simultaneously with mutagenesis, whereas faithful mismatch repair is mostly absent.

► Activation-induced deaminase generates mutagenic uracils in variable genes. ► Uracils are processed by either DNA repair or mutagenic pathways. ► UNG and APE1 proteins participate in both base excision repair and mutagenesis. ► MSH2–MSH6 and EXO proteins participate in both mismatch repair and mutagenesis. ► Base excision repair, but not mismatch repair, occurs during somatic hypermutation.