Nucleic Acids Research Advance Access originally published online on March 12, 2009
Nucleic Acids Research 2009 37(9):2830-2840; doi:10.1093/nar/gkp103
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Nucleic Acids Research, 2009, Vol. 37, No. 9 2830-2840
© Published by Oxford University Press 2009
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Genome Integrity, Repair and Replication |
The efficiency and fidelity of 8-oxo-guanine bypass by DNA polymerases 
and 
1Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences Research, Triangle Park, NC 27709 and 2Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
*To whom correspondence should be addressed. Tel: +1 919 541 2644; Fax: +1 919 541 7613; Email: kunkel{at}niehs.nih.gov
Received November 19, 2008. Revised January 22, 2009. Accepted February 4, 2009.
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.
Present addresses: Scott D. McCulloch, Department of Environmental and Molecular Toxicology, North Carolina State University, Campus Box 7633, Raleigh, NC 27695, USA
Robert J. Kokoska, U.S. Army Research Office, PO Box 12211, Research Triangle Park, NC, USA
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