Lesions Generated by Oxidative Damage to DNA

Polymerase bypass of the mutagenic lesion 8-oxo-G has been studied in considerable detail. All DNA polymerases studied to date insert either dCTP or dATP opposite 8-oxo-G [82-90], Relatively modest decreases in catalytic efficiency have been observed for some polymerases (e.g., around 30-fold decrease for E. coli Pols I and II (exo ), around 10-fold for calf thymus Pol 8), whereas the catalytic efficiency of the model B-family polymerase from bacteriophage T7 (Pol T7) was inhibited around 270-fold as judged by pre-steady-state measurements [83, 85, 86, 91, 92], Only the Y-family polymerases Pol T (from Saccharomyces cerevisiae) and 

Dpo4 (from S. solfataricus) show unaltered or enhanced efficiency when bypassing 8-oxo-G [90, 93], Both of these enzymes bypass 8-oxo-G in a highly accurate manner, with a 20-fold preference for dCTP over dATP. The eukaryotic DinB homolog Pol K is very error-prone when catalyzing nucleotide incorporation opposite 8-oxo-G, showing much greater preference for dATP insertion [58]. 

8-oxo-G, and that base stacking with neighboring base pairs may influence mutagenicity [102]. 

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