Replication inhibition and miscoding properties of a DNA template containing N-(deoxyguanosin-8-yl)-1-aminopyrene (Meeting abstract).

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Replication inhibition and miscoding properties of a DNA template containing N-(deoxyguanosin-8-yl)-1-aminopyrene (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 35:A854 1994. Unique Identifier : AIDSLINE ICDB/94602541
Vyas RR; Basu AK; Dept. of Chemistry, Univ. of Connecticut, Storrs, CT 06269

Abstract: A major DNA adduct formed by the environmental pollutant 1-nitropyrene is N-(deoxyguanosin-8-yl)-1-aminopyrene (dG(AP)). We have synthesized a DNA fragment that contained this adduct at a specific site. A primer was annealed to this template and in vitro DNA synthesis by a variety of polymerases was studied. Primer extension catalyzed by HIV reverse transcriptase, a modified T7 DNA polymerase (Sequenase), human DNA polymerase alpha, or DNA polymerase beta was inhibited almost quantitatively at the base 3' to the adduct site even when high concentration of the polymerase and/or dNTPs were employed. When 3'----5' exonuclease-free Klenow fragment of the DNA polymerase I was used, efficient nucleotide incorporation opposite the adduct was observed. However, dGTP and dATP were preferentially incorporated opposite dG(AP). In the presence of Mg2+, extension beyond the adduct site did not occur. In the presence of Mn2+, on the other hand, significant proportion of the primer was extended to a full-length product. This suggests that dG(AP) can induce both genotoxic and mutagenic effects in vivo.

Keywords: Comparative Study Deoxyguanosine/*ANALOGS & DERIVATIVES/METABOLISM DNA Polymerase I/METABOLISM DNA Polymerase II/METABOLISM DNA Polymerases/*METABOLISM DNA Primers *DNA Replication/DRUG EFFECTS Environmental Pollutants/*TOXICITY Exodeoxyribonucleases/METABOLISM Human HIV/ENZYMOLOGY Pyrenes/*ANALYSIS/METABOLISM/*TOXICITY RNA-Directed DNA Polymerase/*METABOLISM Templates ABSTRACT
941230
M94C4321

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