Somatic hypermutation: activation-induced deaminase for C/G followed by polymerase η for A/T

Abstract

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 η.