Abstract
The cancer drug daunomycin is an effective inhibitor of the B leads to Z transition in poly d(G-C) in 4 M NaCl. Both the rate and extent of the B leads to Z transition are decreased by the drug, as judged by equilibrium and kinetic studies. Daunomycin can, under some conditions, convert Z form DNA back to B form. Drug binding to poly d(G-C) in 4 M NaCl is slow and highly cooperative, consistent with a role for daunomycin as an allosteric effector on the B leads to Z equilibrium. Since daunomycin binds preferentially to alternating purine-pyrimidine sequences, which are the very sequences capable of undergoing the B leads to Z transition, these effects may be an important part of the mechanism by which the drug inhibits transcription and replication.
Full text
PDF









Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arnott S., Chandrasekaran R., Birdsall D. L., Leslie A. G., Ratliff R. L. Left-handed DNA helices. Nature. 1980 Feb 21;283(5749):743–745. doi: 10.1038/283743a0. [DOI] [PubMed] [Google Scholar]
- Behe M., Zimmerman S., Felsenfeld G. Changes in the helical repeat of poly(dG-m5dC) . poly(dG-m5dC) and poly(dG-dC) . poly(dG-dC) associated with the B-Z transition. Nature. 1981 Sep 17;293(5829):233–235. doi: 10.1038/293233a0. [DOI] [PubMed] [Google Scholar]
- Chaires J. B., Dattagupta N., Crothers D. M. Studies on interaction of anthracycline antibiotics and deoxyribonucleic acid: equilibrium binding studies on interaction of daunomycin with deoxyribonucleic acid. Biochemistry. 1982 Aug 17;21(17):3933–3940. doi: 10.1021/bi00260a005. [DOI] [PubMed] [Google Scholar]
- Chaires J. B. Equilibrium studies on the interaction of daunomycin with deoxypolynucleotides. Biochemistry. 1983 Aug 30;22(18):4204–4211. doi: 10.1021/bi00287a007. [DOI] [PubMed] [Google Scholar]
- Dattagupta N., Hogan M., Crothers D. M. Interaction of netropsin and distamycin with deoxyribonucleic acid: electric dichroism study. Biochemistry. 1980 Dec 23;19(26):5998–6005. doi: 10.1021/bi00567a009. [DOI] [PubMed] [Google Scholar]
- Di Marco A., Zunino F., Silverstrini R., Gambarucci C., Gambetta R. A. Interaction of some daunomycin derivatives with deoxyribonucleic acid and their biological activity. Biochem Pharmacol. 1971 Jun;20(6):1323–1328. doi: 10.1016/0006-2952(71)90365-0. [DOI] [PubMed] [Google Scholar]
- Fritzsche H., Triebel H., Chaires J. B., Dattagupta N., Crothers D. M. Studies on interaction of anthracycline antibiotics and deoxyribonucleic acid: geometry of intercalation of iremycin and daunomycin. Biochemistry. 1982 Aug 17;21(17):3940–3946. doi: 10.1021/bi00260a006. [DOI] [PubMed] [Google Scholar]
- HARTMANN G., GOLLER H., KOSCHEL K., KERSTEN W., KERSTEN H. HEMMUNG DER DNA-ABHAENGIGEN RNA- UND DNA-SYNTHESE DURCH ANTIBIOTICA. Biochem Z. 1964 Dec 7;341:126–128. [PubMed] [Google Scholar]
- Haniford D. B., Pulleyblank D. E. Facile transition of poly[d(TG) x d(CA)] into a left-handed helix in physiological conditions. Nature. 1983 Apr 14;302(5909):632–634. doi: 10.1038/302632a0. [DOI] [PubMed] [Google Scholar]
- Lipps H. J., Nordheim A., Lafer E. M., Ammermann D., Stollar B. D., Rich A. Antibodies against Z DNA react with the macronucleus but not the micronucleus of the hypotrichous ciliate stylonychia mytilus. Cell. 1983 Feb;32(2):435–441. doi: 10.1016/0092-8674(83)90463-4. [DOI] [PubMed] [Google Scholar]
- McGhee J. D., von Hippel P. H. Theoretical aspects of DNA-protein interactions: co-operative and non-co-operative binding of large ligands to a one-dimensional homogeneous lattice. J Mol Biol. 1974 Jun 25;86(2):469–489. doi: 10.1016/0022-2836(74)90031-x. [DOI] [PubMed] [Google Scholar]
- Mirau P. A., Kearns D. R. The effect of intercalating drugs on the kinetics of the B to Z transition of poly(dG-dC). Nucleic Acids Res. 1983 Mar 25;11(6):1931–1941. doi: 10.1093/nar/11.6.1931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mitra C. K., Sarma M. H., Sarma R. H. Left-handed deoxyribonucleic acid double helix in solution. Biochemistry. 1981 Mar 31;20(7):2036–2041. doi: 10.1021/bi00510a046. [DOI] [PubMed] [Google Scholar]
- 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]
- Nordheim A., Rich A. The sequence (dC-dA)n X (dG-dT)n forms left-handed Z-DNA in negatively supercoiled plasmids. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1821–1825. doi: 10.1073/pnas.80.7.1821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nordheim A., Tesser P., Azorin F., Kwon Y. H., Möller A., Rich A. Isolation of Drosophila proteins that bind selectively to left-handed Z-DNA. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7729–7733. doi: 10.1073/pnas.79.24.7729. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patel D. J., Kozlowski S. A., Nordheim A., Rich A. Right-handed and left-handed DNA: studies of B- and Z-DNA by using proton nuclear Overhauser effect and P NMR. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1413–1417. doi: 10.1073/pnas.79.5.1413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pilet J., Leng M. Comparison of poly(dG-dC).poly(dG-dC) conformations in oriented films and in solution. Proc Natl Acad Sci U S A. 1982 Jan;79(1):26–30. doi: 10.1073/pnas.79.1.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Quigley G. J., Wang A. H., Ughetto G., van der Marel G., van Boom J. H., Rich A. Molecular structure of an anticancer drug-DNA complex: daunomycin plus d(CpGpTpApCpG). Proc Natl Acad Sci U S A. 1980 Dec;77(12):7204–7208. doi: 10.1073/pnas.77.12.7204. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Singleton C. K., Klysik J., Wells R. D. Conformational flexibility of junctions between contiguous B- and Z-DNAs in supercoiled plasmids. Proc Natl Acad Sci U S A. 1983 May;80(9):2447–2451. doi: 10.1073/pnas.80.9.2447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Tsai C. C., Jain S. C., Sobell H. M. X-ray crystallographic visualization of drug-nucleic acid intercalative binding: structure of an ethidium-dinucleoside monophosphate crystalline complex, Ethidium: 5-iodouridylyl (3'-5') adenosine. Proc Natl Acad Sci U S A. 1975 Feb;72(2):628–632. doi: 10.1073/pnas.72.2.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vorlíckovă M., Kypr J., Stokrová S., Sponar J. A Z-like form of poly(dA-dC).poly(dG-dT) in solution? Nucleic Acids Res. 1982 Feb 11;10(3):1071–1080. doi: 10.1093/nar/10.3.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Ward D. C., Reich E., Goldberg I. H. Base specificity in the interaction of polynucleotides with antibiotic drugs. Science. 1965 Sep 10;149(3689):1259–1263. doi: 10.1126/science.149.3689.1259. [DOI] [PubMed] [Google Scholar]
- Wu H. M., Dattagupta N., Crothers D. M. Solution structural studies of the A and Z forms of DNA. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6808–6811. doi: 10.1073/pnas.78.11.6808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zimmer C., Marck C., Guschlbauer W. Z-DNA and other non-B-DNA structures are reversed to B-DNA by interaction with netropsin. FEBS Lett. 1983 Apr 5;154(1):156–160. doi: 10.1016/0014-5793(83)80894-1. [DOI] [PubMed] [Google Scholar]
- Zimmer C., Tymen S., Marck C., Guschlbauer W. Conformational transitions of poly(dA-dC).poly(dG-dT) induced by high salt or in ethanolic solution. Nucleic Acids Res. 1982 Feb 11;10(3):1081–1091. doi: 10.1093/nar/10.3.1081. [DOI] [PMC free article] [PubMed] [Google Scholar]
