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. Author manuscript; available in PMC: 2020 Jun 1.
Published in final edited form as: Prog Nucl Magn Reson Spectrosc. 2019 May 11;112-113:55–102. doi: 10.1016/j.pnmrs.2019.05.002

Figure 38.

Figure 38.

Watson-Crick-like G-T mismatches and their roles in generating spontaneous mutations during DNA replication. A) Kinetic topology for transforming between G-T/U wobble mismatches and their Watson-Crick-like counterparts formed via tautomerization or ionization. The exchange rates shown were obtained using NMR RD measurements[195, 197]. B) Minimal kinetic model for Watson-Crick BP incorporation by DNA polymerases. The incorporation of a G-T mismatch requires in addition, as shown in the lower pathway, a tautomerization or ionization step allowing for the formation of a Watson-Crick-like species.(Bottom left) Histograms showing Fpol, the fidelity of dTTP/5BrdUTP mis-incorporation errors catalyzed by Alfalfa Mosaic Virus Reverse Transcriptase (AMV RT) as computed using kinetic simulations allowing incorporation of tautomeric (blue, MES1), ionic (green, MES2) or both (orange, MES1 + MES2) Watson-Crick-like excited states, and experimentally measured values (gray).(Bottom right) Measured and simulated rates (kobs) of mis-incorporation for dTTP/5BrdUTP catalyzed by human DNA polymerase β. Reprinted by permission from [195].