Nucleic Acids Research, 2000, Vol. 28, No. 21 4138-4146
© 2000 Oxford University Press
Error-free and error-prone lesion bypass by human DNA polymerase 
in vitro
Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA, 1Department of Chemistry, Washington University, St Louis, MO 63130, USA and 2Chemistry Department, New York University, New York, NY 10003, USA
Error-free lesion bypass and error-prone lesion bypass are important cellular responses to DNA damage during replication, both of which require a DNA polymerase (Pol). To identify lesion bypass DNA polymerases, we have purified human Pol
encoded by the DINB1 gene and examined its response to damaged DNA templates. Here, we show that human Pol is a novel lesion bypass polymerase in vitro. Purified human Pol efficiently bypassed a template 8-oxoguanine, incorporating mainly A and less frequently C opposite the lesion. Human Pol most frequently incorporated A opposite a template abasic site. Efficient further extension required T as the next template base, and was mediated mainly by a one-nucleotide deletion mechanism. Human Pol was able to bypass an acetylaminofluorene-modified G in DNA, incorporating either C or T, and less efficiently A opposite the lesion. Furthermore, human Pol effectively bypassed a template (–)-trans-anti-benzo[a]pyrene-N2-dG lesion in an error-free manner by incorporating a C opposite the bulky adduct. In contrast, human Pol was unable to bypass a template TT dimer or a TT (6-4) photoproduct, two of the major UV lesions. These results suggest that Pol plays an important role in both error-free and error-prone lesion bypass in humans.
* To whom correspondence should be addressed. Tel: +1 859 323 5784; Fax: +1 859 323 1059; Email: zwang@pop.uky.edu
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