Somatic hypermutation: subverted DNA repair.
Somatic hypermutation generates high-affinity antibodies of different isotypes that efficiently protect us against a plethora of pathogens. Recent analyses of the types of mutations produced in gene-deficient mice have indicated how DNA repair proteins are drawn into the pathway. Activation-induced cytosine deaminase begins the process by deaminating cytosine to uracil in DNA. The uracils are then recognized by the base excision repair protein uracil DNA glycosylase and by the mismatch repair proteins MutS homologue 2 and MutS homologue 6. Instead of repairing the uracils, these proteins attract low fidelity DNA polymerases, which synthesize nucleotide substitutions at an unprecedented level.
Martomo
Stella A
SA
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Gearhart
Patricia J
PJ
D000818:Animals; D004247:DNA / Q000235:genetics* / Q000276:immunology; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000502:physiology; D007134:Immunoglobulin Switch Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D009154:Mutation; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics* / Q000276:immunology; D051981:Uracil-DNA Glycosidase / Q000502:physiology
D004268:DNA-Binding Proteins; D007135:Immunoglobulin Variable Region; D004247:DNA; D051981:Uracil-DNA Glycosidase