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Influence of minor groove binders on the eukaryotic topoisomerase II cleavage reaction with 41 base pair model oligonucleotides

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Summary

This report deals with the cleavage reaction of calf thymus (CT) topoisomerase II with oligonucleotides containing one main cleavage site and adjacent binding sites for minor groove binders. The sequences of the oligonucleotides were derived from a pBR 322 sequence, which contains one main topoisomerase II cleavage site. The cleavage reaction was performed under increasing concentrations of minor groove binders and it showed characteristic inhibition dependences of topoisomerase II to the binding sites and to the binding length of the minor groove binders. The extension of the minor groove binder length on DNA from 4 to 10 base pairs (bp) by netropsin and bis-netropsin, respectively, causes a strong increase of the topoisomerase II cleavage inhibition. The same is observed by the introduction of a second minor groove binder sequence symmetrically positioned around the topoisomerase II main cleavage site. The combination of two different minor groove binders can lead to an increased topoisomerase II inhibition but also to a prevention of total inhibition as shown with chromomycin A3 and distamycin A at concentrations of 0.1 and 0.25 μM, respectively.

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References

  1. Geliert M: DNA topoisomerases. Annu Rev Biochem 50:879–910, 1981

    Article  PubMed  Google Scholar 

  2. Wang JC: DNA topoisomerases. Annu Rev Biochem 54:665–697, 1985

    Article  PubMed  Google Scholar 

  3. Wang JC: DNA topoisomerases: why so many? J Biol Chem 266:6659–6662, 1991

    PubMed  Google Scholar 

  4. Roca J, Wang JC: DNA transport by a type II DNA topoisomerase: evidence in favor of a two-gate mechanism. Cell 77:609–161, 1994

    PubMed  Google Scholar 

  5. Roca J: The mechanisms of DNA topoisomerases. TIBS 20:156–160, 1995

    PubMed  Google Scholar 

  6. Thomson B, Bednixen C, Lund K, Andersen AH, Sørensen BS, Westergaard O: Characterization of the interaction between topoisomerase II and DNA by transcriptional footprinting. J Mol Biol 215:237–244, 1990

    PubMed  Google Scholar 

  7. Spitzner JR, Chung JK, Muller MT: Eucaryotic topoisomerase II preferentially cleaves alternating purinepyrimidine repeats. Nucl Acids Res 18:1–11, 1989

    Google Scholar 

  8. Lund K, Andersen AH, Christiansen K, Svejstrup JW, Westergaard O: Minimal DNA requirement for topoisomerase II-mediated cleavage in vitro. J Biol Chem 265: 13856–13863, 1990

    PubMed  Google Scholar 

  9. Sander M, Hsieh T-S: Double strand DNA cleavage by type II DNA topoisomerase from drosophila melanogaster. J Biol Chem 258:8421–8428, 1983

    PubMed  Google Scholar 

  10. Liu LF, Rowe TC, Yang L, Tewey KM, Chen GL: Cleavage of DNA by mammalian DNA topoisomerase II. J Biol Chem 258:15365–15370, 1983

    PubMed  Google Scholar 

  11. Nelson EM, Tewey KM, Liu LF: Mechanism of antitumor drug action: poisoning of mammalian DNA topoisomerase II on DNA by 4′-(9-acridinylamino)-methanesulfon-m-aniside. Proc Nat Acad Sci USA 81: 1361–1365, 1984

    PubMed  Google Scholar 

  12. Maxwell A, Geliert M: Mechanistic aspects of DNA topoisomerases. In: Afinsen CB, Edsall JT, Richards FM (eds) Advan Protein Chem 38. Academic Press, inc., 1986, pp. 69–107

  13. Sørensen BS, Sinding J, Andersen AH, Alsner J, Jensen PB, Westergaard O: Mode of action of topoisomerase II-targeting agents at a specific DNA sequence: uncoupling the DNA binding, cleavage and religation events. J Biol Chem 228:778–786, 1992

    Google Scholar 

  14. Liu LF: DNA topoisomerase poisons as antitumor drugs. Ann Rev Biochem 58:351–375, 1989

    Article  PubMed  Google Scholar 

  15. D'Arpa P, Liu LF: Topoisomerase-targeting antitumor drugs. Biochim Biophys Acta 989:163–177, 1989

    PubMed  Google Scholar 

  16. Waring MJ: DNA modification and cancer. Ann Rev Biochem 50:159–192, 1981

    PubMed  Google Scholar 

  17. Zimmer C: Effects of the antibiotics netropsin and distamycin A on the structure and function of nucleic acids. Prog Nucleic Acid Res Mol Biol 15:285–318, 1975

    PubMed  Google Scholar 

  18. Gilbert DE, Feigon J: Structural analysis of drug-DNA interactions. Curr Opin Struct Biol 1:439–445, 1991

    Google Scholar 

  19. Zimmer C, Wähnert U: Nonintercalating DNA-binding ligands: Specificity of the interaction and their use as tools in biophysical, biochemical and biological investigations of the genetic material. Progr Biophys molec Biol 47:31–112, 1986

    Google Scholar 

  20. Neidle S, Pearl LH, Skelly JV: DNA structure and perturbation by drug binding. Biochem J 243:1–13, 1987

    PubMed  Google Scholar 

  21. Simon H, Wittig B, Zimmer C: Effect of netropsin, distamycin A and chromomycin A3 on the binding and cleavage reaction of DNA gyrase. FEES Lett 353:79–83, 1994

    Google Scholar 

  22. Beerman TA, Woynarowski JM, Sigmund RD, Gawron LS, Rao KE, Lown JW: Netropsin and bis-netropsin analogs as inhibitors of the catalytic activity of mammalian DNA topoisomerase II and topoisomerase cleavable complexes. Biochim Biophys Acta 1090:52–60, 1991

    PubMed  Google Scholar 

  23. Rao KE, Krowicki K, Balzarini J, De Clercq E, Newman RA, Lown JW: Novel linked antiviral and antitumor agents related to netropsin-2: synthesis and biological evaluation. Actual Chim Thér 18:21–42, 1991

    Google Scholar 

  24. Chen AY, Yu C, Gatto Liu LF: DNA minor groove binding ligands: a different class of mammalian DNA topoisomerase I inhibitors. Proc Nat Acad Sci USA 90:8131–8135, 1993

    PubMed  Google Scholar 

  25. Lown JW: DNA recognition by lexitropsins, minor groove binding agents. J Mol Recogn 7:79–88, 1994

    Google Scholar 

  26. Gao X, Patel DJ: Solution structure of the chromomycin-DNA complex. Biochemistry 28:751–762, 1989

    PubMed  Google Scholar 

  27. Banville DL, Keniry MA, Kam M, Shafer RH: NMR studies of the interaction of chromomycin A3 with small DNA duplexes: binding to GC-containing sequences. Biochemistry 29:6521–6534, 1990

    PubMed  Google Scholar 

  28. Itzhaki L, Weinberger S, Livnah N, Berman E: A unique binding cavity for divalent cations in the DNA-metalchromomycin A3 complex. Biopolymers 29:481–489, 1990

    PubMed  Google Scholar 

  29. Gao X, Mirau P, Patel DJ: Structure refinement of the chromomycin dimer-DNA oligomer complex in solution. J Mol Biol 223:259–279, 1992

    PubMed  Google Scholar 

  30. Stankus A, Goodisman J, Dabrowiak JC: Quantitative footprinting analysis of the chromomycin A3-DNA interaction. Biochemistry 31:9310–9318, 1992

    PubMed  Google Scholar 

  31. Silva DJ, Kahne D: Chromomycin A3 as a blueprint for designed metal complexes. J Am Chem Soc 116:2641–2642, 1994

    Google Scholar 

  32. Woynarowski JM, McHugh M, Sigmund RD, Beerman TA: Modulation of topoisomerase II catalytic activity by DNA minor groove binding agents distamycin, hoechst 33258, and 4′,6-diamidine-2-phenylindole. Mol Pharmacol 35:177–182, 1989

    PubMed  Google Scholar 

  33. Strausfeld U, Richter A: Simultaneous purification of DNA topoisomerase I and II from eukaryotic cells. Prep Biochem 19:37–48, 1989

    PubMed  Google Scholar 

  34. Andersen AH, Sørensen BS, Christiansen K, Svejstrup JQ, Lund K, Westergaard O: Studies of the topoisomerase II-mediated cleavage and religation reactions by use of a suicidal double-stranded DNA substrate. J Biol Chem 266:9203–9210, 1991

    PubMed  Google Scholar 

  35. Hesse G, Geller K: Untersuchungen zur Phosphorbestimmung (Nukleotidphosphor) nach Hurst mit einem SnCl2/Hydrazinsulfatreagenz. Mikrochim Acta (Wien): 526–533, 1968

  36. Kissinger KL, Dabrowiak JC, Lown JW: Molecular recognition between oligopeptides and nucleic acids: DNA binding specificity of a series of bis netropsin analogues deduced from footprinting analysis. Chem Res Toxicol 3:162–168, 1990

    PubMed  Google Scholar 

  37. Keniry MA, Banville DL, Simmonds PM, Shafer R: Nuclear magnetic resonance comparison of the binding sites of mithramycin and chromomycin on the self-complementary oligonucleotide d(ACCCGGGT)2: evidence that the saccharide chains have a role in sequence specificity. J Mol Biol 231:753–767, 1993

    PubMed  Google Scholar 

  38. Lin C, Chen FM: Oligonucleotide studies of sequence-specific binding of chromomycin A3 to DNA. Biochemistry 33:1419–1424, 1994

    PubMed  Google Scholar 

  39. Portugal J, Waring MJ: Assignment of DNA binding sites for 4′,6-diamidine-2-phenylindole and bisbenzimide (Hoechst 33258): a comparative footprinting study. Biochim Biophys Acta 949:158–168, 1988

    PubMed  Google Scholar 

  40. Wilson WD, Tanious FA, Barton HJ, Jones RL, Fox K, Wydra RL, Strekowski L: DNA-sequence dependent binding modes of 4′,6-diamidino-2-phenylindole (DAPI). Biochemistry 29:8452–8461, 1990

    PubMed  Google Scholar 

  41. Mortensen UH, Stevnsner T, Krogh S, Olesen K, Westergaard O, Bonven BJ: Distamyicn inhibition of topoisomerase I-DNA interaction: a mechanistic analysis. Nucl Acids Res 18:1983–1989, 1990

    PubMed  Google Scholar 

  42. Pelton JG, Wemmer DE: Structural characterization of a 2∶1 distamycin A.d(CGCAAATTGGC) complex by two-dimensional NMR. Proc Nat Acad Sci USA 86:5723–5727, 1989

    PubMed  Google Scholar 

  43. Chen X, Ramakrishnan B, Rao ST, Sundaralingam M: Binding of two distamycin A molecules in the minor groove of an alternating B-DNA duplex. Nat Struct biol 1:169–175, 1994

    PubMed  Google Scholar 

  44. Geierstanger BH, Mrksich M, Dervan PB, Wemmer DE: Design of a G.C-specific DNA minor groove-binding peptide. Science 266:646–650, 1994

    PubMed  Google Scholar 

  45. Kopka ML, Yoon C, Goodsell D, Pjura P, Dickerson RE: The molecular origin of DNA-drug specificity in netropsin and distamycin. Proc Nat Acad Sci USA 82:1376–1380, 1985

    PubMed  Google Scholar 

  46. Coll M, Frederick CA, Wang AH-J, Rich A: A bifurcated hydrogen-bonded conformation in the d(A.T) base pairs of the DNA dodecamer d(CGCAAATTTGCG) and its complex with distamycin. Proc Nat Acad Sci USA 84: 8385–8389, 1987

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Institut für Molekulare Biotechnologie e.V., Beutenbergstr. 11, D-07745, Jena, Germany

    Achim Bell, Leonhard Kittler & Günter Löber

  2. Institut für Molekularbiologie, Friedrich-Schiller-Universität Jena, Winzerlaer Str. 10, D-07745, Jena, Germany

    Christoph Zimmer

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  1. Achim Bell
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  2. Leonhard Kittler
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  3. Günter Löber
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  4. Christoph Zimmer
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Bell, A., Kittler, L., Löber, G. et al. Influence of minor groove binders on the eukaryotic topoisomerase II cleavage reaction with 41 base pair model oligonucleotides. Invest New Drugs 13, 271–284 (1995). https://doi.org/10.1007/BF00873133

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