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. 1984 Jul 11;12(13):5429–5439. doi: 10.1093/nar/12.13.5429

Two rotameric forms of open ring 7-methylguanine are present in alkylated polynucleotides.

S Boiteux, J Belleney, B P Roques, J Laval
PMCID: PMC318929  PMID: 6462910

Abstract

High performance liquid chromatography analysis of imidazole open ring 7-methylguanine, 2-6 diamino-4-hydroxy-5N-methyl-formamidopyrimidine (rom7G), showed two well-separated peaks (fI and fII) of the same magnitude. Rechromatography of each isolated component indicated that they are slowly interconverted to give a 1:1 mixture. NMR analysis demonstrated that the two species observed on reversed phase HPLC are rotational isomers. Thermodynamic measurements strongly suggested that the equilibrium can be assigned to rotation around the N-methyl formamido bond. The two species, fI and fII, separated by HPLC were identified as rotamers E and Z, respectively. The structures of fI and fII were also determined. A polynucleotide containing rom7G was obtained by alkaline treatment of poly (dGC) containing 7-methylguanine. In order to study its structure within the polynucleotide, rom7G was enzymatically excized by E.coli rom7G-DNA glycosylase. The analysis of the products released by the enzyme showed a 1:4 mixture of the two rotamers favoring the Z form (fII).

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beranek D. T., Weis C. C., Evans F. E., Chetsanga C. J., Kadlubar F. F. Identification of N5-methyl-N5-formyl-2,5,6-triamino-4-hydroxypyrimidine as a major adduct in rat liver DNA after treatment with the carcinogens, N,N-dimethylnitrosamine or 1,2-dimethylhydrazine. Biochem Biophys Res Commun. 1983 Jan 27;110(2):625–631. doi: 10.1016/0006-291x(83)91195-6. [DOI] [PubMed] [Google Scholar]
  2. Boiteux S., Laval J. Imidazole open ring 7-methylguanine: an inhibitor of DNA synthesis. Biochem Biophys Res Commun. 1983 Jan 27;110(2):552–558. doi: 10.1016/0006-291x(83)91185-3. [DOI] [PubMed] [Google Scholar]
  3. Chetsanga C. J., Lindahl T. Release of 7-methylguanine residues whose imidazole rings have been opened from damaged DNA by a DNA glycosylase from Escherichia coli. Nucleic Acids Res. 1979 Aug 10;6(11):3673–3684. doi: 10.1093/nar/6.11.3673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chetsanga C. J., Lozon M., Makaroff C., Savage L. Purification and characterization of Escherichia coli formamidopyrimidine-DNA glycosylase that excises damaged 7-methylguanine from deoxyribonucleic acid. Biochemistry. 1981 Sep 1;20(18):5201–5207. doi: 10.1021/bi00521a016. [DOI] [PubMed] [Google Scholar]
  5. Karran P., Lindahl T., Ofsteng I., Evensen G. B., Seeberg E. Escherichia coli mutants deficient in 3-methyladenine-DNA glycosylase. J Mol Biol. 1980 Jun 15;140(1):101–127. doi: 10.1016/0022-2836(80)90358-7. [DOI] [PubMed] [Google Scholar]
  6. Laval J., Pierre J., Laval F. Release of 7-methylguanine residues from alkylated DNA by extracts of Micrococcus luteus and Escherichia coli. Proc Natl Acad Sci U S A. 1981 Feb;78(2):852–855. doi: 10.1073/pnas.78.2.852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Laval J. Two enzymes are required from strand incision in repair of alkylated DNA. Nature. 1977 Oct 27;269(5631):829–832. doi: 10.1038/269829a0. [DOI] [PubMed] [Google Scholar]
  8. Lawley P. D., Orr D. J. Specific excision of methylation products from DNA of Escherichia coli treated with N-methyl-N'-nitro-N-nitrosoguanidine. Chem Biol Interact. 1970 Aug;2(2):154–157. doi: 10.1016/0009-2797(70)90047-5. [DOI] [PubMed] [Google Scholar]
  9. Lawley P. D., Shah S. A. Methylation of ribonucleic acid by the carcinogens dimethyl sulphate, N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Comparisons of chemical analyses at the nucleoside and base levels. Biochem J. 1972 Jun;128(1):117–132. doi: 10.1042/bj1280117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lindahl T. DNA repair enzymes. Annu Rev Biochem. 1982;51:61–87. doi: 10.1146/annurev.bi.51.070182.000425. [DOI] [PubMed] [Google Scholar]
  11. Loveless A. Possible relevance of O-6 alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosamides. Nature. 1969 Jul 12;223(5202):206–207. doi: 10.1038/223206a0. [DOI] [PubMed] [Google Scholar]
  12. Margison G. P., Pegg A. E. Enzymatic release of 7-methylguanine from methylated DNA by rodent liver extracts. Proc Natl Acad Sci U S A. 1981 Feb;78(2):861–865. doi: 10.1073/pnas.78.2.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Roques B. P., Garbay-Jaureguiberry C., Combrisson S., Oberlin R. Determination of the rates and barriers to conformational isomerization in the dipeptide L-Pro-L-4Hyp by direct 13C NMR thermal equilibration. Biopolymers. 1977 Apr;16(4):937–944. doi: 10.1002/bip.1977.360160415. [DOI] [PubMed] [Google Scholar]
  14. Singer B. The chemical effects of nucleic acid alkylation and their relation to mutagenesis and carcinogenesis. Prog Nucleic Acid Res Mol Biol. 1975;15(0):219–284. [PubMed] [Google Scholar]

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