The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20062409
The Journal of Experimental Medicine, Vol. 204, No. 1, 7-10
The Rockefeller University Press, 0022-1007 $30.00
© Neuberger et al.
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COMMENTARY

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

Michael S. Neuberger and Cristina Rada

CORRESPONDENCE M.S.N.: msn{at}mrc-lmb.cam.ac.uk


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 {eta}.

M.S. Neuberger and C. Rada are at Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, UK


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