Misincorporation of dNTPs opposite 1,N2-ethenoguanine and 5,6,7,9-tetrahydro-7-hydroxy-9-oxoimidazo[1,2-a]purine in oligonucleotides by Escherichia coli polymerases I exo- and II exo-, T7 polymerase exo-, human immunodeficiency virus-1 reverse transcriptase, and rat polymerase beta

Biochemistry
S LangouëtF P Guengerich

Abstract

1,N2-Ethenoguanine (1,N2-epsilon-Gua) and 5,6,7,9-tetrahydro-7-hydroxy-9-oxoimidazo[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. The oligonucleotides (19-mers), 5'-CAGTGGGTG*TCCGAATTGA-3', were prepared, with each of these modified bases substituted for G at G*. HO-ethanodeoxyguanosine exists predominantly as a mixture of diastereomers of the closed cyclic hemiaminal form, 5,6,7,9-tetrahydro-7-hydroxy-9-oxoimidazo[1,2-a]purine, shown by H2(18)O experiments to be in equilibrium with the open form, N2-(2-oxoethyl)Gua. Both adducts retarded the 3'-extension of a complementary 10-mer primer by all of the polymerases examined, but in every case, some full-length product was obtained. Nucleotide sequence analysis indicated misincorporation of dGTP and dATP across from both 1,N2-epsilon-Gua and HO-ethanoGua, with the extent varying considerably among the polymerases. Similar results were obtained when the abilities of the polymerases to incorporate a single dNTP were evaluated. In addition, -1 and -2 base frame shifts were detected with both 1,N2-epsilon-Gua and HO-ethanoGua with some of the polymerases. Steady-state kinetic experiments...Continue Reading

References

Nov 5, 1987·Journal of Molecular Biology·J M ClarkG P Beardsley
Jan 1, 1984·CRC Critical Reviews in Biochemistry·N J Leonard
Jan 1, 1993·Annual Review of Biochemistry·K A Johnson

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Citations

Nov 26, 2003·Mutation Research·Laurent GrosMurat Saparbaev
Dec 3, 2003·Mutation Research·Glaucia R MartinezPaolo Di Mascio
Apr 26, 2003·Mutation Research·Anja SchaeferhenrichBeatrice Louise Pool-Zobel
Mar 5, 1999·Mutation Research·J NairH Bartsch
Oct 12, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Hasan Koc, James A Swenberg
Jun 20, 2006·Chemical Research in Toxicology·Jeong-Yun ChoiF Peter Guengerich
Jul 31, 2007·Chemical Research in Toxicology·Min Young KimGerald N Wogan
Oct 19, 2007·Chemical Research in Toxicology·Ganesh ShanmugamMichael P Stone
Oct 31, 2009·Carcinogenesis·Nidhi ShrivastavJohn M Essigmann
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·B HangB Singer
Feb 28, 2004·FEBS Letters·Sabrina A MarquesMarisa H G Medeiros
Apr 11, 2012·Angewandte Chemie·Linlin ZhaoF Peter Guengerich
Jan 20, 2012·Free Radical Research·Alicja WinczuraBarbara Tudek
Nov 21, 2007·Journal of Molecular Biology·Alexandra DimitriDavid A Scicchitano
Dec 3, 2016·Free Radical Biology & Medicine·Barbara TudekElżbieta Speina
Feb 4, 2005·Environmental and Molecular Mutagenesis·Priscilla H FernandesR Stephen Lloyd
Aug 1, 2002·Current Protocols in Toxicology·James A SwenbergPatricia B Upton
Dec 29, 2019·The Journal of Biological Chemistry·Adam Z Thelen, Patrick J O'Brien
Aug 8, 2019·DNA Repair·Jennifer KayBevin Engelward
Jan 25, 2021·The Journal of Biological Chemistry·Adam Z Thelen, Patrick J O'Brien
Mar 13, 2019·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Mark M MuenterPenny J Beuning
Aug 13, 2008·Chemical Research in Toxicology·Ganesh ShanmugamMichael P Stone
Feb 9, 2006·Chemical Reviews·F Peter Guengerich
Mar 26, 1999·Journal of Medicinal Chemistry·S KhullarF Johnson
Jun 17, 2021·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·F Peter Guengerich, Pratibha P Ghodke

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