Nucleic Acids Research, 2002, Vol. 30, No. 23 5284-5292
© 2002 Oxford University Press
Translesion replication of benzo[a]pyrene and benzo[c]phenanthrene diol epoxide adducts of deoxyadenosine and deoxyguanosine by human DNA polymerase 
Section on DNA Replication, Repair, and Mutagenesis, Building 6, Room 1A13, National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-2725 USA, 1 Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0820, USA and 2 Institute for Virus Research, Kyoto University, Sakyo, Kyoto 606-8507, Japan
*To whom correspondence should be addressed. Tel: +1 301 496 6175; Fax: +1 301 594 1135; Email: woodgate{at}helix.nih.gov
Human DNA polymerase 
(pol) is a Y-family polymerase whose cellular function is presently unknown. Here, we report on the ability of pol to bypass various stereoisomers of benzo[a]pyrene (BaP) diol epoxide (DE) and benzo[c]phenanthrene (BcPh) DE adducts at deoxyadenosine (dA) or deoxyguanosine (dG) bases in four different template sequence contexts in vitro. We find that the BaP DE dG adducts pose a strong block to pol-dependent replication and result in a high frequency of base misincorporations. In contrast, misincorporations opposite BaP DE and BcPh DE dA adducts generally occurred with a frequency ranging between 2 x 10–3 and 6 x 10–4. Although dTMP was inserted efficiently opposite all dA adducts, further extension was relatively poor, with one exception (a cis opened adduct derived from BcPh DE) where up to 58% extension past the lesion was observed. Interestingly, another human Y-family polymerase, pol
, was able to extend dTMP inserted opposite a BaP DE dA adduct. We suggest that pol might therefore participate in the error-free bypass of DE-adducted dA in vivo by predominantly incorporating dTMP opposite the damaged base. In many cases, elongation would, however, require the participation of another polymerase more specialized in extension, such as pol.
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