The efficiency and fidelity of 8-oxo-guanine bypass by DNA polymerases delta and eta

A DNA lesion created by oxidative stress is 7,8-dihydro-8-oxo-guanine (8-oxoG). Because 8-oxoG can mispair with adenine during DNA synthesis, it is of interest to understand the efficiency and fidelity of 8-oxoG bypass by DNA polymerases. We quantify bypass parameters for two DNA polymerases implicated in 8-oxoG bypass, Pols d and g. Yeast Pol d and yeast Pol g both bypass 8-oxoG and misincorporate adenine during bypass. However, yeast Pol g is 10-fold more efficient than Pol d, and following bypass Pol g switches to less processive synthesis, similar to that observed during bypass of a cis-syn thymine-thymine dimer. Moreover, yeast Pol g is at least 10-fold more accurate than yeast Pol d during 8-oxoG bypass. These differences are maintained in the presence of the accessory proteins RFC, PCNA and RPA and are consistent with the established role of Pol g in suppressing ogg1-dependent mutagenesis in yeast. Surprisingly different results are obtained with human and mouse Pol g. Both mammalian enzymes bypass 8-oxoG efficiently, but they do so less processively, without a switch point and with much lower fidelity than yeast Pol g. The fact that yeast and mammalian Pol g have intrinsically different catalytic properties has potential biological implications.