Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1983 Jun 25;11(12):4185–4193. doi: 10.1093/nar/11.12.4185

The incorporation of O6-methyldeoxyguanosine and O4-methyldeoxythymidine monophosphates into DNA by DNA polymerases I and alpha.

J A Hall, R Saffhill
PMCID: PMC326033  PMID: 6866769

Abstract

The modified nucleoside 5'-triphosphates O6-MedGTP ad O4-MedTTP have been synthesised and their acceptability as DNA-precursors investigated using DNA polymerases I and alpha in an in vitro assay. O6-MedGMP is only incorporated into newly-synthesized DNA-like material in the presence of templates containing thymine bases. Similarly O4-MedTMP is only incorporated in the presence of templates containing guanine bases. The results confirm the promutagenic nature and base-pairing properties of O6-MeG ad O4-MeT.

Full text

PDF
4185

Selected References

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

  1. Abbott P. J., Mehta J. R., Ludlum D. B. Synthesis of 8-14C-labeled O6-methyldeoxyguanosine and its deoxynucleotide copolymers. Biochemistry. 1980 Feb 19;19(4):643–647. doi: 10.1021/bi00545a006. [DOI] [PubMed] [Google Scholar]
  2. Abbott P. J., Saffhill R. DNA synthesis with methylated poly(dC-dG) templates. Evidence for a competitive nature to miscoding by O(6)-methylguanine. Biochim Biophys Acta. 1979 Mar 28;562(1):51–61. doi: 10.1016/0005-2787(79)90125-4. [DOI] [PubMed] [Google Scholar]
  3. Abbott P. J., Saffhill R. DNA-synthesis with methylated poly(dA-dT) templates: possible role of O4-methylthymine as a pro-mutagenic base. Nucleic Acids Res. 1977 Mar;4(3):761–769. doi: 10.1093/nar/4.3.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brennand J., Saffhill R., Fox M. The effects of methylated thymidines upon cultures of V79 cells and the mechanism of incorporation of O4-methylthymidine into their DNA. Carcinogenesis. 1982;3(2):219–222. doi: 10.1093/carcin/3.2.219. [DOI] [PubMed] [Google Scholar]
  5. EIDINOFF M. L., CHEONG L., RICH M. A. Incorporation of unnatural pyrimidine bases into deoxyribonucleic acid of mammalian cells. Science. 1959 Jun 5;129(3362):1550–1551. doi: 10.1126/science.129.3362.1550. [DOI] [PubMed] [Google Scholar]
  6. Engel J. D., von Hippel P. H. D(M6ATP) as a probe of the fidelity of base incorporation into polynucleotides by Escherichia coli DNA polymerase I. J Biol Chem. 1978 Feb 10;253(3):935–939. [PubMed] [Google Scholar]
  7. Gautschi J. R., Burkhalter M., Baumann E. A. Comparative utilization of bromodeoxyuridine and iododeoxyuridine triphosphates for mammalian DNA replication in vitro. Biochim Biophys Acta. 1978 Mar 29;518(1):31–36. doi: 10.1016/0005-2787(78)90113-2. [DOI] [PubMed] [Google Scholar]
  8. Gerchman L. L., Ludlum D. B. The properties of O 6 -methylguanine in templates for RNA polymerase. Biochim Biophys Acta. 1973 May 10;308(2):310–316. doi: 10.1016/0005-2787(73)90160-3. [DOI] [PubMed] [Google Scholar]
  9. HOARD D. E., OTT D. G. CONVERSION OF MONO- AND OLIGODEOXYRIBONUCLEOTIDES TO 5-TRIPHOSPHATES. J Am Chem Soc. 1965 Apr 20;87:1785–1788. doi: 10.1021/ja01086a031. [DOI] [PubMed] [Google Scholar]
  10. Hendler S., Fürer E., Srinivasan P. R. Synthesis and chemical properties of monomers and polymers containing 7-methylguanine and an investigation of their substrate or template properties for bacterial deoxyribonucleic acid or ribonucleic acid polymerases. Biochemistry. 1970 Oct 13;9(21):4141–4153. doi: 10.1021/bi00823a017. [DOI] [PubMed] [Google Scholar]
  11. LEPAGE G. A. Incorporation of 6-thioguanine into nucleic acids. Cancer Res. 1960 Apr;20:403–408. [PubMed] [Google Scholar]
  12. Lawley P. D., Orr D. J., Shah S. A., Farmer P. B., Jarman M. Reaction products from N-methyl-N-nitrosourea and deoxyribonucleic acid containing thymidine residues. Synthesis and identification of a new methylation product, O4-methylthymidine. Biochem J. 1973 Sep;135(1):193–201. doi: 10.1042/bj1350193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Mehta J. R., Ludlum D. B. Synthesis and properties of O6-methyldeoxyguanylic acid and its copolymers with deoxycytidylic acid. Biochim Biophys Acta. 1978 Dec 21;521(2):770–778. doi: 10.1016/0005-2787(78)90316-7. [DOI] [PubMed] [Google Scholar]
  15. Miller C. T., Lawley P. D., Shah S. A. Cellular reactions of O6-methylguanine, a product of some alkylating carcinogens. Biochem J. 1973 Oct;136(2):387–393. doi: 10.1042/bj1360387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Newbold R. F., Warren W., Medcalf A. S., Amos J. Mutagenicity of carcinogenic methylating agents is associated with a specific DNA modification. Nature. 1980 Feb 7;283(5747):596–599. doi: 10.1038/283596a0. [DOI] [PubMed] [Google Scholar]
  17. Pegg A. E., Swann P. F. Metabolism of O6-alkyldeoxyguanosines and their effect on removal of O6-methylguanine from rat liver DNA. Biochim Biophys Acta. 1979 Dec 17;565(2):241–252. doi: 10.1016/0005-2787(79)90202-8. [DOI] [PubMed] [Google Scholar]
  18. Singer B., Fraenkel-Conrat H., Kuśmierek J. T. Preparation and template activities of polynucleotides containing O2- and O4-alkyluridine. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1722–1726. doi: 10.1073/pnas.75.4.1722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sági J. T., Szabolcs A., Szemzö A., Otvös L. Modified polynucleotides. I. Investigation of the enzymatic polymerization of 5-alkyl-dUTP-s. Nucleic Acids Res. 1977 Aug;4(8):2767–2777. doi: 10.1093/nar/4.8.2767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. TRAUTNER T. A., SWARTZ M. N., KORNBERG A. Enzymatic synthesis of deoxyribonucleic acid. X. Influence of bromouracil substitutions on replication. Proc Natl Acad Sci U S A. 1962 Mar 15;48:449–455. doi: 10.1073/pnas.48.3.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yoshida S., Yamada M., Masaki S., Saneyoshi M. Utilization of 2'-deoxy-6-thioguanosine 5'-triphosphate in DNA synthesis in vitro by DNA polymerase alpha from calf thymus. Cancer Res. 1979 Oct;39(10):3955–3958. [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES