Nucleic Acids Research, 2000, Vol. 28, No. 23 4717-4724
© 2000 Oxford University Press
Error-prone lesion bypass by human DNA polymerase 
Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA, 1Chemistry Department, New York University, New York, NY 10003, USA and 2Department of Chemistry, Washington University, St Louis, MO 63130, USA
DNA lesion bypass is an important cellular response to genomic damage during replication. Human DNA polymerase 
(Pol), encoded by the Xeroderma pigmentosum variant (XPV) gene, is known for its activity of error-free translesion synthesis opposite a TT cis-syn cyclobutane dimer. Using purified human Pol, we have examined bypass activities of this polymerase opposite several other DNA lesions. Human Pol efficiently bypassed a template 8-oxoguanine, incorporating an A or a C opposite the lesion with similar efficiencies. Human Pol effectively bypassed a template abasic site, incorporating an A and less frequently a G opposite the lesion. Significant –1 deletion was also observed when the template base 5' to the abasic site is a T. Human Pol partially bypassed a template (+)-trans-anti-benzo[a]pyrene-N2-dG and predominantly incorporated an A, less frequently a T, and least frequently a G or a C opposite the lesion. This specificity of nucleotide incorporation correlates well with the known mutation spectrum of (+)-trans-anti-benzo[a]pyrene-N2-dG lesion in mammalian cells. These results show that human Pol is capable of error-prone translesion DNA syntheses in vitro and suggest that Pol may bypass certain lesions with a mutagenic consequence in humans.
* To whom correspondence should be addressed. Tel: +1 859 323 5784; Fax: +1 859 323 1059; Email: zwang{at}pop.uky.edu
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