The efficiency and fidelity of 8-oxo-guanine bypass by DNA polymerases δ and η

Scott D. Mcculloch, Robert J. Kokoska, Parie Garg, Peter M. Burgers, Thomas A. Kunkel

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

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

Original languageEnglish
Pages (from-to)2830-2840
Number of pages11
JournalNucleic acids research
Volume37
Issue number9
DOIs
StatePublished - 2009

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