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. 1983 Mar 25;11(6):1931–1941. doi: 10.1093/nar/11.6.1931

The effect of intercalating drugs on the kinetics of the B to Z transition of poly(dG-dC).

P A Mirau, D R Kearns
PMCID: PMC325847  PMID: 6835844

Abstract

We have measured the ability of the intercalating drugs proflavine, ethidium bromide, actinomycin D, and bismethidiumspermine to inhibit the salt induced transition of poly(dG-dC) from the B to the Z form. While all of the drugs studied slowed the B to Z transition, the effectiveness of the drugs correlates much better with their DNA binding kinetics than their DNA binding constants. In studies where the binding densities of ethidium and actinomycin were varied we have found that high levels of ethidium, more than 1 per 20 base pairs, were required to inhibit the B to Z transition while low levels of actinomycin, less than 1 per 450 base pairs, reduced the transition rate. Studies of the B to Z transition in the presence of both actinomycin and ethidium suggest that the drugs inhibit the transition by different mechanisms. The results are interpreted in terms of a modification of the kinetic model proposed by Pohl and Jovin in which, depending on the DNA binding kinetics of the drug, the drug may inhibit nucleation and/or propagation of the B to Z transition.

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Selected References

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

  1. Behe M., Felsenfeld G. Effects of methylation on a synthetic polynucleotide: the B--Z transition in poly(dG-m5dC).poly(dG-m5dC). Proc Natl Acad Sci U S A. 1981 Mar;78(3):1619–1623. doi: 10.1073/pnas.78.3.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bresloff J. L., Crothers D. M. DNA-ethidium reaction kinetics: demonstration of direct ligand transfer between DNA binding sites. J Mol Biol. 1975 Jun 15;95(1):103–123. doi: 10.1016/0022-2836(75)90339-3. [DOI] [PubMed] [Google Scholar]
  3. Crawford J. L., Kolpak F. J., Wang A. H., Quigley G. J., van Boom J. H., van der Marel G., Rich A. The tetramer d(CpGpCpG) crystallizes as a left-handed double helix. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4016–4020. doi: 10.1073/pnas.77.7.4016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ivanov V. I., Minyat E. E. The transitions between left- and right-handed forms of poly(dG-dC). Nucleic Acids Res. 1981 Sep 25;9(18):4783–4798. doi: 10.1093/nar/9.18.4783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kłysik J., Stirdivant S. M., Larson J. E., Hart P. A., Wells R. D. Left-handed DNA in restriction fragments and a recombinant plasmid. Nature. 1981 Apr 23;290(5808):672–677. doi: 10.1038/290672a0. [DOI] [PubMed] [Google Scholar]
  6. Li H. J., Crothers D. M. Relaxation studies of the proflavine-DNA complex: the kinetics of an intercalation reaction. J Mol Biol. 1969 Feb 14;39(3):461–477. doi: 10.1016/0022-2836(69)90138-7. [DOI] [PubMed] [Google Scholar]
  7. Möller A., Nordheim A., Nichols S. R., Rich A. 7-Methylguanine in poly(dG-dC).poly(dG-dC) facilitates z-DNA formation. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4777–4781. doi: 10.1073/pnas.78.8.4777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Müller W., Crothers D. M. Studies of the binding of actinomycin and related compounds to DNA. J Mol Biol. 1968 Jul 28;35(2):251–290. doi: 10.1016/s0022-2836(68)80024-5. [DOI] [PubMed] [Google Scholar]
  9. Nordheim A., Pardue M. L., Lafer E. M., Möller A., Stollar B. D., Rich A. Antibodies to left-handed Z-DNA bind to interband regions of Drosophila polytene chromosomes. Nature. 1981 Dec 3;294(5840):417–422. doi: 10.1038/294417a0. [DOI] [PubMed] [Google Scholar]
  10. Patel D. J., Canuel L. L., Pohl F. M. "Alternating B-DNA" conformation for the oligo(dG-dC) duplex in high-salt solution. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2508–2511. doi: 10.1073/pnas.76.6.2508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Pohl F. M., Jovin T. M., Baehr W., Holbrook J. J. Ethidium bromide as a cooperative effector of a DNA structure. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3805–3809. doi: 10.1073/pnas.69.12.3805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pohl F. M., Jovin T. M. Salt-induced co-operative conformational change of a synthetic DNA: equilibrium and kinetic studies with poly (dG-dC). J Mol Biol. 1972 Jun 28;67(3):375–396. doi: 10.1016/0022-2836(72)90457-3. [DOI] [PubMed] [Google Scholar]
  13. Pohl F. M. Polymorphism of a synthetic DNA in solution. Nature. 1976 Mar 25;260(5549):365–366. doi: 10.1038/260365a0. [DOI] [PubMed] [Google Scholar]
  14. Thamann T. J., Lord R. C., Wang A. H., Rich A. The high salt form of poly(dG-dC).poly(dG-dC) is left-handed Z-DNA: Raman spectra of crystals and solutions. Nucleic Acids Res. 1981 Oct 24;9(20):5443–5457. doi: 10.1093/nar/9.20.5443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Wang A. H., Quigley G. J., Kolpak F. J., Crawford J. L., van Boom J. H., van der Marel G., Rich A. Molecular structure of a left-handed double helical DNA fragment at atomic resolution. Nature. 1979 Dec 13;282(5740):680–686. doi: 10.1038/282680a0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Wells R. D., Goodman T. C., Hillen W., Horn G. T., Klein R. D., Larson J. E., Müller U. R., Neuendorf S. K., Panayotatos N., Stirdivant S. M. DNA structure and gene regulation. Prog Nucleic Acid Res Mol Biol. 1980;24:167–267. doi: 10.1016/s0079-6603(08)60674-1. [DOI] [PubMed] [Google Scholar]
  18. Wing R., Drew H., Takano T., Broka C., Tanaka S., Itakura K., Dickerson R. E. Crystal structure analysis of a complete turn of B-DNA. Nature. 1980 Oct 23;287(5784):755–758. doi: 10.1038/287755a0. [DOI] [PubMed] [Google Scholar]
  19. van de Sande J. H., Jovin T. M. Z* DNA, the left-handed helical form of poly[d(G-C)] in MgCl2-ethanol, is biologically active. EMBO J. 1982;1(1):115–120. doi: 10.1002/j.1460-2075.1982.tb01133.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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