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.
Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States.
Huseyin
H
Saribasak
Patricia J
PJ
Gearhart
D000818:Animals; D004247:DNA / Q000235:genetics / Q000276:immunology*; D004260:DNA Repair; D006801:Humans; D016296:Mutagenesis; D027041:Somatic Hypermutation, Immunoglobulin
D004247:DNA