The efficiency and fidelity of 8-oxo-guanine bypass by DNA polymerases  and 

ISSN： 1362-4962

Source： Nucleic Acids Research, Vol.37, Iss.9, 2009-05, pp. : 2830-2840

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Abstract

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  and . Yeast Pol  and yeast Pol  both bypass 8-oxoG and misincorporate adenine during bypass. However, yeast Pol  is 10-fold more efficient than Pol , and following bypass Pol  switches to less processive synthesis, similar to that observed during bypass of a cis-syn thymine-thymine dimer. Moreover, yeast Pol  is at least 10-fold more accurate than yeast Pol  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  in suppressing ogg1-dependent mutagenesis in yeast. Surprisingly different results are obtained with human and mouse Pol . 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 . The fact that yeast and mammalian Pol  have intrinsically different catalytic properties has potential biological implications.