Somatic hypermutation: activation-induced deaminase for C/G followed by polymerase eta for A/T.
Somatic hypermutation (SHM) introduces nucleotide substitutions into immunoglobulin variable (Ig V) region genes at all four bases, but the mutations at C/G and A/T pairs are achieved by distinct mechanisms. Mutations at C/G pairs are a direct consequence of the C-->U deamination catalyzed by activation-induced deaminase (AID). Mutations at A/T pairs, however, require a second mutagenic process that occurs during patch repair of the AID-generated U/G mismatch. Several DNA polymerases have been proposed to play a role in SHM, but accumulating evidence indicates that the mutations at A/T are overwhelmingly achieved by recruitment of DNA polymerase eta.
Neuberger
Michael S
MS
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK. msn@mrc-lmb.cam.ac.uk
Rada
Cristina
C
D000818:Animals; D020029:Base Pairing; D003564:Cytidine Deaminase / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D027041:Somatic Hypermutation, Immunoglobulin; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000099270:Y-Family DNA Polymerases
D003564:Cytidine Deaminase; D004247:DNA; D004259:DNA-Directed DNA Polymerase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases