Misincorporation of dNTPs opposite 1,N2-ethenoguanine and 5,6,7,9-tetrahydro-7-hydroxy-9-oxo-imidazo[1,2-a]purine in oligonucleotides by Escherichia coli polymerases I exo- and II exo-, T7 polymerase exo-, HIV-1 reverse transcriptase, and rat polymerase beta (Meeting abstract). NLM AIDSLINE Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

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Misincorporation of dNTPs opposite 1,N2-ethenoguanine and 5,6,7,9-tetrahydro-7-hydroxy-9-oxo-imidazo[1,2-a]purine in oligonucleotides by Escherichia coli polymerases I exo- and II exo-, T7 polymerase exo-, HIV-1 reverse transcriptase, and rat polymerase beta (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 38:A251 1997. Unique Identifier : AIDSLINE MED/97619044
Langouet S; Muller M; Guengerich FP; Department of Biochemistry and Center in Molecular Toxicology,; Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Abstract: 1,N2-etheno(epsilon)guanine(Gua) and 5,6,7,9-tetrahydro-7-hydroxy-9-oxo-imidazo[1,2-a]purine HO-ethanoGua) are two modified bases formed in the reaction of DNA with 2-chlorooxirane the epoxide derivative of vinyl chloride. Both adducts incorporated in oligonucleotides retarded the 3'-extension of a complementary 10-mer primer by all five polymerases (pols) but in every case some full-length product was obtained. Nucleotide sequence analysis as well as single base incorporation studies indicated misincorporation of dGTP and dATP across from both 1,N2-epsilon-Gua and HO-ethanoGua with the extent varying considerably among the pols. Also -1 and -2 base frameshifts were detected with both 1,N2-epsilon-Gua and HO-ethanoGua with some of the pols. Steady-state kinetic experiments with Escherichia coli pol I exo- and T7 pol exo- showed large decreases in kcat for all dNTP incorporations compared to the normal G:dCTP pair and high misincorporation frequencies for dATP and dGTP with both adducts. The results indicate that the 1,N2-epsilon-Gua and HO-ethanoGua adducts have considerable miscoding potential.
Keywords: *DNA-Directed DNA Polymerase/CHEMISTRY *Escherichia coli/ENZYMOLOGY *Guanine/ANALOGS & DERIVATIVES *Imidazoles/CHEMISTRY *Nucleotides/CHEMISTRY *Purines/CHEMISTRYKWDdna-directeddnapolymerase/chemistryKWDescherichiacoli/enzymologyKWDguanine/analogs&derivativesKWDimidazoles/chemistryKWDnucleotides/chemistryKWDpurines/chemistry
971030
M97A1340

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