Opinion -: Somatic hypermutation at A•T pairs:: polymerase error versus dUTP incorporation

Somatic hypermutation of immunoglobulin genes occurs at both C.G pairs and A.T pairs. Mutations at C.G pairs are created by activation-induced deaminase (AID)-catalysed deamination of C residues to U residues. Mutations at A.T pairs are probably produced during patch repair of the AID-generated U.G lesion, but they occur through an unknown mechanism. Here, we compare the popular suggestion of nucleotide mispairing through polymerase error with an alternative possibility, mutation through incorporation of dUTP (or another non-canonical nucleotide).