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. 1987 Aug 25;15(16):6539–6552. doi: 10.1093/nar/15.16.6539

Visualization of an AAF induced frameshift mutation: molecular views of base displacement in B-DNA from minimized potential energy calculations.

S Broyde, B E Hingerty
PMCID: PMC306121  PMID: 3627997

Abstract

Energy minimized structures of base displacement in an AAF modified B-DNA dodecamer are presented. A rational search strategy, beginning with a global search of the conformation space of the modified deoxydinucleoside monophosphate, together with model building by computer graphics, has been employed. A number of different minimum energy conformations have been located which reveal base displaced structures. These show fluorene interstrand stacking, fluorene inter- and intrastrand stacking, and non-stacked fluorene situated in the denatured bulge. The local helix axis is bent to various extents in the different forms, and one or two base pairs are fully denatured. One structure of special interest offers a molecular view that suggests how AAF can induce the -2 deletion mutation observed in AAF modified E. coli.

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Selected References

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

  1. Altona C., Sundaralingam M. Conformational analysis of the sugar ring in nucleosides and nucleotides. A new description using the concept of pseudorotation. J Am Chem Soc. 1972 Nov 15;94(23):8205–8212. doi: 10.1021/ja00778a043. [DOI] [PubMed] [Google Scholar]
  2. Beranek D. T., White G. L., Heflich R. H., Beland F. A. Aminofluorene-DNA adduct formation in Salmonella typhimurium exposed to the carcinogen N-hydroxy-2-acetylaminofluorene. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5175–5178. doi: 10.1073/pnas.79.17.5175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berman H. M., Neidle S., Stodola R. K. Drug-nucleic acid interactions: conformational flexibility at the intercalation site. Proc Natl Acad Sci U S A. 1978 Feb;75(2):828–832. doi: 10.1073/pnas.75.2.828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bichara M., Fuchs R. P. DNA binding and mutation spectra of the carcinogen N-2-aminofluorene in Escherichia coli. A correlation between the conformation of the premutagenic lesion and the mutation specificity. J Mol Biol. 1985 Jun 5;183(3):341–351. doi: 10.1016/0022-2836(85)90005-1. [DOI] [PubMed] [Google Scholar]
  5. Broyde S., Hingerty B. An internal fluorene model for iodo-N-2-acetylaminofluorene modified DNA. Chem Biol Interact. 1983 Oct 15;47(1):69–78. doi: 10.1016/0009-2797(83)90148-5. [DOI] [PubMed] [Google Scholar]
  6. Broyde S., Hingerty B. Base displacement in AAF-modified Z-DNA. Carcinogenesis. 1985 Jan;6(1):151–154. doi: 10.1093/carcin/6.1.151. [DOI] [PubMed] [Google Scholar]
  7. Broyde S., Hingerty B. The influence of terminal 3', 5' phosphates on conformations of dApdA. Nucleic Acids Res. 1979;6(6):2165–2178. doi: 10.1093/nar/6.6.2165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carothers A. M., Urlaub G., Steigerwalt R. W., Chasin L. A., Grunberger D. Characterization of mutations induced by 2-(N-acetoxy-N-acetyl)aminofluorene in the dihydrofolate reductase gene of cultured hamster cells. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6519–6523. doi: 10.1073/pnas.83.17.6519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chang C. T., Miller S. J., Wetmur J. G. Physical studies of N-acetoxy-N-2-acetylaminofluorene-modified deoxyribonucleic acid. Biochemistry. 1974 May 7;13(10):2142–2148. doi: 10.1021/bi00707a023. [DOI] [PubMed] [Google Scholar]
  10. Drew H. R., Wing R. M., Takano T., Broka C., Tanaka S., Itakura K., Dickerson R. E. Structure of a B-DNA dodecamer: conformation and dynamics. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2179–2183. doi: 10.1073/pnas.78.4.2179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Evans F. E., Levine R. A. Conformation and configuration at the central amine nitrogen of a nucleotide adduct of the carcinogen 2-(acetylamino)fluorene as studied by 13C and 15N NMR spectroscopy. J Biomol Struct Dyn. 1986 Apr;3(5):923–934. doi: 10.1080/07391102.1986.10508474. [DOI] [PubMed] [Google Scholar]
  12. Fuchs R. P., Lefevre J. F., Pouyet J., Daune M. P. Comparative orientation of the fluorene residue in native DNA modified by N-acetoxy-N-2-acetylaminofluorene and two 7-halogeno derivatives. Biochemistry. 1976 Jul 27;15(15):3347–3351. doi: 10.1021/bi00660a027. [DOI] [PubMed] [Google Scholar]
  13. Fuchs R., Daune M. Physical studies on deoxyribonucleic acid after covalent binding of a carcinogen. Biochemistry. 1972 Jul 4;11(14):2659–2666. doi: 10.1021/bi00764a017. [DOI] [PubMed] [Google Scholar]
  14. Grunberger D., Nelson J. H., Cantor C. R., Weinstein I. B. Coding and conformational properties of oligonucleotides modified with the carcinogen N-2-acetylaminofluorene. Proc Natl Acad Sci U S A. 1970 Jun;66(2):488–494. doi: 10.1073/pnas.66.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hanau L. H., Santella R. M., Grunberger D., Erlanger B. F. An immunochemical examination of acetylaminofluorene-modified poly(dG-dC) X poly(dG-dC) in the Z-conformation. J Biol Chem. 1984 Jan 10;259(1):173–178. [PubMed] [Google Scholar]
  16. Hartman P. E., Ames B. N., Roth J. R., Barnes W. M., Levin D. E. Target sequences for mutagenesis in Salmonella histidine-requiring mutants. Environ Mutagen. 1986;8(4):631–641. doi: 10.1002/em.2860080414. [DOI] [PubMed] [Google Scholar]
  17. Hingerty B. E., Broyde S. Carcinogen-base stacking and base-base stacking in dCpdG modified by (+) and (-) anti-BPDE. Biopolymers. 1985 Dec;24(12):2279–2299. doi: 10.1002/bip.360241209. [DOI] [PubMed] [Google Scholar]
  18. Hingerty B. E., Broyde S. Energy minimized structures of carcinogen-DNA adducts: 2-acetylaminofluorene and 2-aminofluorene. J Biomol Struct Dyn. 1986 Dec;4(3):365–372. doi: 10.1080/07391102.1986.10506355. [DOI] [PubMed] [Google Scholar]
  19. Hingerty B., Broyde S. Conformation of the deoxydinucleoside monophosphate dCpdG modified at carbon 8 of guanine with 2-(acetylamino)fluorene. Biochemistry. 1982 Jun 22;21(13):3243–3252. doi: 10.1021/bi00256a034. [DOI] [PubMed] [Google Scholar]
  20. Koffel-Schwartz N., Verdier J. M., Bichara M., Freund A. M., Daune M. P., Fuchs R. P. Carcinogen-induced mutation spectrum in wild-type, uvrA and umuC strains of Escherichia coli. Strain specificity and mutation-prone sequences. J Mol Biol. 1984 Jul 25;177(1):33–51. doi: 10.1016/0022-2836(84)90056-1. [DOI] [PubMed] [Google Scholar]
  21. Mitchell N., Stöhrer G. Mutagenesis originating in site-specific DNA damage. J Mol Biol. 1986 Sep 20;191(2):177–180. doi: 10.1016/0022-2836(86)90254-8. [DOI] [PubMed] [Google Scholar]
  22. Neidle S., Kuroda R., Broyde S., Hingerty B. E., Levine R. A., Miller D. W., Evans F. E. Studies on the conformation and dynamics of the C8-substituted guanine adduct of the carcinogen acetylaminofluorene; model for a possible Z-DNA modified structure. Nucleic Acids Res. 1984 Nov 12;12(21):8219–8233. doi: 10.1093/nar/12.21.8219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shakked Z., Rabinovich D., Kennard O., Cruse W. B., Salisbury S. A., Viswamitra M. A. Sequence-dependent conformation of an A-DNA double helix. The crystal structure of the octamer d(G-G-T-A-T-A-C-C). J Mol Biol. 1983 May 15;166(2):183–201. doi: 10.1016/s0022-2836(83)80005-9. [DOI] [PubMed] [Google Scholar]
  24. Stellman S. D., Hingerty B., Broyde S. B., Subramanian E., Sato T., Langridge R. Structure of guanosine-3',5'-cytidine monophosphate. I. Semi-empirical potential energy calculations and model-building. Biopolymers. 1973 Dec;12(12):2731–2750. doi: 10.1002/bip.1973.360121208. [DOI] [PubMed] [Google Scholar]
  25. Wang A. J., Quigley G. J., Kolpak F. J., van der Marel G., van Boom J. H., Rich A. Left-handed double helical DNA: variations in the backbone conformation. Science. 1981 Jan 9;211(4478):171–176. doi: 10.1126/science.7444458. [DOI] [PubMed] [Google Scholar]

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