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. Author manuscript; available in PMC: 2015 Oct 23.
Published in final edited form as: DNA Repair (Amst). 2004 Jan 5;3(1):85–89. doi: 10.1016/j.dnarep.2003.09.008

Figure 1. A Model for Somatic Hypermutations.

Figure 1

The stepwise processing of DNA by AID and other enzymes is shown schematically. The first row of steps (Phase I) followed by the filling-in of the one nucleotide gap in DNA by a (relatively) error-free DNA polymerase to restore a C•G pair is the normal base excision repair pathway for DNA repair. This creates no mutations. If no repair occurs (Phase II, Left), the uracil is fixed as thymine during replication causing a C to T mutation. The intermediate in this pathway, U•G, is unlikely to be subject to mismatch correction. If the abasic site created by the removal of uracil is copied by a lesion bypass polymerase (LBP; Phase II, Center), then mutations are introduced in the bottom (G containing) strand. The incorrectly paired bases introduced by LBPs are represented by X, Y and Z and this SHM pathway is labeled as “A”. The intermediates in this pathway may be subjected to further processing by the cell including mismatch correction. If the gap created by the actions of an AP endonuclease and a dRPase at the abasic site is filled-in by an LBP (Phase II, Right), mutations are introduced in the top (C containing) strand. This is labeled as SHM pathway “B”. The intermediates in this pathway may also be subject to mismatch correction. In some earlier publications [24,25] Phase I was distinguished from Phase II only by the presence of mismatch correction during the latter stage. However, lesion bypass is likely to be coupled with mismatch correction and hence these two processes have been combined together in Phase II in my model. This is a minimal model for SHM because it does not attempt to explain many of the well-documented features of somatic hypermutations in detail- mutations at non-C•G pairs, for example.