Alteration of Dna Structure: The Common Result of the Interaction Between DNA and Physical and Chemical Agents

  • G. Ciarrocchi
  • A. Montecucco
  • G. Pedrali-Noy
  • S. Spadari


It is becoming evident that the majority, if not all, of mutagens and carcinogens bind, either covalently or not, to nucleic acids or induce chemical modifications in these target molecules. This interaction seems critical in both mutagenic and carcinogenic processes. Since the alterations in nucleic acid structure are likely to have functional consequences, it is important to gain a better understanding of the modifications in the target structure.


Twist Angle Pyrimidine Dimer Thymine Dimer Diammine Dichloroplatinum Cesium Chloride Density Gradient 
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  1. Benham, C.J., 1981, Theoretical analysis of competitive conformational transitions in torsionally stressed DNA, J. Mol. Biol.150: 43–68.PubMedCrossRefGoogle Scholar
  2. Camerman, N., and Camerman, A., 1968, Photodimer of thymine in ultraviolet-irradiated DNA: proof of structure by X-ray diffraction, Science, 160: 1451–1452.PubMedCrossRefGoogle Scholar
  3. Ciarrocchi, G. and Pedrini, A.M., 1982, Determination of pyrimidine dimer unwinding angle by measurement of DNA electrophoretic mobility, J. Mol. Biol.155: 177–183.PubMedCrossRefGoogle Scholar
  4. Ciarrocchi, G. and Southerland, B.M., 1983, Irradiation of circular DNA with 254 nm radiation or sensitization in the presence of Ag+: evidence for unwinding by photoproducts other than pyrimidine dimers, Photochem. Photobiol.38: 259–263.PubMedCrossRefGoogle Scholar
  5. Ciarrocchi, G., Sutherland, B.M. and Pedrini, A.M., 1982, Photoreversal of DNA unwinding caused by pyrimidine dimers.Biochimie64: 665–668.PubMedCrossRefGoogle Scholar
  6. Ciomei, M., Spadari, S., Pedrali-Noy, G. and Ciarrocchi, G., 1984, Structural alterations of pathologically or physiologically modified DNA.Nucleic Acid Res.12: 1977–1989.PubMedCrossRefGoogle Scholar
  7. Denhart, D.J. and Kato, A.C., 1973, Comparison of the effect of ultraviolet radiation and ethidium bromide intercalation on the conformation of superhelical oX174 replicative form DNA.J. Mol. Biol.77: 479–494.CrossRefGoogle Scholar
  8. Dickerson, R.E., Drew, H.R., Concer B.N., Kopka M.L. and Pjuva, P.E., 1983, Helix geometry and hidration in A-DNA, B-DNA and Z-DNA.Cold Spring Harbor Symp. Quant. Biol.47: 13–24.Google Scholar
  9. Dickson, R.C., Abelson, J., Barnes, W.M. and Reznikoff, W.S., 1975, Genetic regulation: thelaccontrol region.Science187: 27–35.PubMedCrossRefGoogle Scholar
  10. Drinkwater, N.R., Miller, J.A., Miller, E.C. and Yang, N.-C., 1978, Covalent intercalative binding to DNA in relation to the mutagenicity of hydro carbon epoxides and N-acetoxy-2-acetylaminofluorene.Cancer Res.38: 3247–3255.PubMedGoogle Scholar
  11. Gamper, H.B. and Hearst, J.E., 1982, A topological model for transcription based on unwinding angle analysis ofE. coliRNA polymerase binary, initiation and ternary complexe.Cell29: 81–90.PubMedCrossRefGoogle Scholar
  12. Gamper, H.B., Straub, K., Calvin, M. and Bartholomew, J.C., 1980, DNA alkylation and unwinding induced by benzo(a)pyrene diolepoxide: modulation by ionic strength and superhelicity.Proc. Natl. Acad. Sci.USA 77: 2000–2004.PubMedCrossRefGoogle Scholar
  13. Kabsch, W., Sander, C., and Trifonov, E.N., 1982, The 10 helical twist angles of B-DNA.Nucleic Acids Res.10: 1097–1104.PubMedCrossRefGoogle Scholar
  14. Kahn, M., 1974, The effect of thymine dimers on DNA:DNA hybridization.Biopolymers13: 669.PubMedCrossRefGoogle Scholar
  15. Keller, W. and Wendell, I., 1974, Stepwise relaxation of supercoiled SV40 DNA 39:199–208.Google Scholar
  16. Kim, R. and Kim, S.-H, 1983, Direct measurement of DNA unwinding angle in specific interaction between lac operator and repressor.Cold Spring Harbor Symp. Quant. Biol.47: 451–454.PubMedGoogle Scholar
  17. Kim, S-H, Peckler, S., Graves, B., Kanne, D., Rapoport, H. and Hearst, J.E., 1983, Sharp kink of DNA at psoralen-cross-link site deduced from crystal structure of psoralen-thymine monoadduct.Cold Spring Harbor Symp. Quant. Biol.47: 361–365.PubMedGoogle Scholar
  18. Hayes, F.N., Williams, R.L., Ratliff, R.L., Varghese, A.J., and Rupert, C.S., 1971, Effect of a single thymine photodimer on the oligo- deoxythymidilate-polydeoxyadenilate interaction.J. Am. Chem. Soc.93: 4940–4942.PubMedCrossRefGoogle Scholar
  19. Lan, P., and Gray, H., 1979 Extracellular nucleases ofAlteromonas espejianaBAL 31. IV. The single strand-specific deoxiriboendo nuclease activity as a probe for regions of altered secondary structure in negatively and positively supercoiled closed circular DNA.Nucleic Acids Res.6: 331–357.Google Scholar
  20. Lilley, D., 1980, The inverted repeat as a recognizable structural feature in supercoiled DNA molecules.Proc. Natl. Acad. Sci. U.S.A.77: 6468–6472.PubMedCrossRefGoogle Scholar
  21. Malcolm, A.D.B., and Shnounou, G., 1983, Netropsin increases the linking number of DNA.Cold Spring Harbor Symp. Quant. Biol.47, 323–326.PubMedGoogle Scholar
  22. Maniatis, T. and Ptashne, M., 1973, Multiple repressor binding at the operators in bacteriophage lambda.Proc. Natl. Acad. Sci. U.S.A.70: 1535–1531.Google Scholar
  23. Meehan, T., Gamper, H. and Becker J.F., 1982, Characterization of reversible, physical binding of benzo(a)pyrene derivatives to DNA.J. Biol. Chem.257: 10479–10485.PubMedGoogle Scholar
  24. Merkel, C.M. and Lippard, S.J. (1983) Ethidium bromide alters the binding mode of cis-diammine dichloroplatinum(II) to pBR322 DNA.Cold Spring Harbor Symp. Quant. Biol.47: 355–360.PubMedGoogle Scholar
  25. Pearlman, D.A., Hoibrook, S.R., Pirkle, D.H. and Kim, S-H, 1985, Molecular models for DNA damaged by photoreaction.Science227: 1304–1308.PubMedCrossRefGoogle Scholar
  26. Pedrini, A.M. and Ciarrocchi, G., 1983, Inhibition of Micrococcus luteus DNA topoisomerase I by UV photoproducts.Proc. Natl. Acad. Sci. U.S.A., 80: 1787–1791.PubMedCrossRefGoogle Scholar
  27. Regan, J.D., and Setlow, R.B., 1974, Two forms of repair in the DNA of human cells damaged by chemical carcinogens and mutagens.Cancer Res., 34: 3318–3325.PubMedGoogle Scholar
  28. Register, J.C., Sperrazza, J.M. and Griffith, J., 1983, RecA protein unwinds douplex DNA by 180 degrees for every 17 base pairs in the fiber formed with ATP S.UCLA Symposia on Molecular and Cellular Biology, 10: 731–738.Google Scholar
  29. Sangalli, S., Rebuzzini, A., Spadari, S., Pedrali-Noy, G., Focher, F., and Ciarrocchi, G., 1984, Methylation of UV-irradiated and chemically modified DNAs.Medecine Biologie Environnement, 12: 527–530.Google Scholar
  30. Scowell, W.M. and Collart, F., 1985, Unwinding of supercoiled DNA by cis- and trans-diammineichloroplatinum(II): influence of the torsional strain on DNA unwinding.Nucleic Acids Res., 13: 2881–2895.CrossRefGoogle Scholar
  31. Shafranovskaya, N.N., Trifonov, E.N., Lazurkin, Yu.S. and Franck-Kamenetskii, M.D., 1973, Clustering of the thymine dimers in ultraviolet irradiated DNA and the long-range transfer of electronic excitation along the molecule.Nature241: 58–60.Google Scholar
  32. Spadari, S., Pedrali-Noy, G., Ciomei, M., Rebuzzini, A., Hubscher, U., and Ciarrocchi, G., 1984, DNA methylation and DNA structure, pp. 551–556. In: Proteins involved in DNA replication (ed. Ubscher and S. Spadari) Plenum Publishing Corp.Google Scholar
  33. Spadari, S., Pedrali-Noy, G., Focher, F., Montecucco, A., Bordoni, T., Geroni, C., Giuliani, F.C., Ventrella, G., Arcamone, F. and Ciarrocchi, G., 1986, DNA polymerases and topoisomerases as targets for the development of anticancer drugs.Anticancer Res., 6: 935–940.PubMedGoogle Scholar
  34. Triebel, H., Reinert, K.-E., Bar, H. and Lang, H., 1979, Structural changes of ultraviolet-irradiated DNA derived from hydrodynamic measurements.Biochim. Biophys. Acta, 561: 59–68.PubMedGoogle Scholar
  35. Trifonov, E.N. and Sussman, J.L., 1980, The pitch of chromatin DNA is reflected in its nucleotide sequence, Proc. Natl. Acad. Sci, U.S.A., 77: 3816–3820.PubMedCrossRefGoogle Scholar
  36. Vinograd, J., Lebowitz, J. and Watson, R., 1968, Early and late helix-coil transitions in closed circular DNA. The number of superhelical turns in polyoma DNA.J. Mol. Biol.33: 173–197.PubMedCrossRefGoogle Scholar
  37. Vorlickova, M. and Palecek, E., 1978, Changes in properties of DNA caused by gamma and ultraviolet radiation. Dependence of conformational changes on the chemical nature of the damage. Biochim. Biophys. Acta, 517: 308–318.Google Scholar
  38. Wang, J.C.,1974, The degree of unwinding of the DNA helix by ethydium I.titration of twisted PM2 DNA molecules in alkaline cesium chloride density gradients.J. Mol. Biol., 89: 783–801.PubMedCrossRefGoogle Scholar
  39. Wang, J.C., Jacobsen J.H., and Saucier, J.M., 1977, Physicochemical studies on interactions between DNA and RNA polymerase. Unwinding of the DNA helix by Escherichia coli RNA polymerase.Nucleic Acids Res., 4: 1225–1241.PubMedCrossRefGoogle Scholar
  40. Wang, S.Y., 1976, Photochemistry and photobiology of Nucleic Acids, Vol. II, Academic Press, N.Y.Google Scholar
  41. Waring, M.J. and Chisholm, J.W., 1972, Uncoiling of bacteriophage PM2 DNA by binding of steroidal diamines, Biochim. Biophys. Acta, 262: 18–23.PubMedGoogle Scholar
  42. Wiesehahn, G. and Hearst, J.E., 1978, DNA unwinding induced by photoaddition of psoralen derivatives and determination of dark binding equilibrium constants by gel electrophoresis.Proc. Natl. Acad. Sci. U.S.A.75: 2703–2707.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • G. Ciarrocchi
    • 1
  • A. Montecucco
    • 1
  • G. Pedrali-Noy
    • 1
  • S. Spadari
    • 1
  1. 1.Istituto di Genetica Biochimica ed Evoluzionistica del C.N.R.PaviaItaly

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