Nucleic Acids Research, 2001, Vol. 29, No. 4 928-935
© 2001 Oxford University Press
Response of human DNA polymerase 
to DNA lesions
Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA and 1Department of Chemistry, Washington University, St Louis, MO 63130, USA
Lesion bypass is an important mechanism to overcome replication blockage by DNA damage. Translesion synthesis requires a DNA polymerase (Pol). Human Pol 
encoded by the RAD30B gene is a recently identified DNA polymerase that shares sequence similarity to Pol 
. To investigate whether human Pol plays a role in lesion bypass we examined the response of this polymerase to several types of DNA damage in vitro. Surprisingly, 8-oxoguanine significantly blocked human Pol . Nevertheless, translesion DNA synthesis opposite 8-oxoguanine was observed with increasing concentrations of purified human Pol , resulting in predominant C and less frequent A incorporation opposite the lesion. Opposite a template abasic site human Pol efficiently incorporated a G, less frequently a T and even less frequently an A. Opposite an AAF-adducted guanine, human Pol was able to incorporate predominantly a C. In both cases, however, further DNA synthesis was not observed. Purified human Pol responded to a template TT (6–4) photoproduct by inserting predominantly an A opposite the 3' T of the lesion before aborting DNA synthesis. In contrast, human Pol was largely unresponsive to a template TT cis-syn cyclobutane dimer. These results suggest a role for human Pol in DNA lesion bypass.
* 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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