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. 1991 Dec 25;19(24):6725–6730. doi: 10.1093/nar/19.24.6725

Echinomycin binding to alternating AT.

K R Fox 1, J N Marks 1, K Waterloh 1
PMCID: PMC329301  PMID: 1762903

Abstract

We have studied the binding of echinomycin to DNA fragments containing GC-rich regions flanked by blocks of alternating AT by DNase I footprinting and diethylpyrocarbonate modification. Regions of alternating AT flanking the sequences CCCG, CCGC, CGGC and GG show a four base pair DNase I cleavage pattern and reaction of alternate adenines with diethylpyrocarbonate. This pattern is strongest when the AT-block is immediately adjacent to the CpG ligand binding site. We explain these phenomena by suggesting that echinomycin binds to the dinucleotide step ApT in a cooperative fashion. The cooperative effects can be transmitted through the dinucleotide step GC but not CC or AA. No such repetitive patterns are seen with surrounding regions of (ATT).(AAT). Evidence is presented for secondary drug binding sites at CpC and TpG with weaker interaction at the CpG site within the hexanucleotide TTCGAA.

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Selected References

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

  1. Cons B. M., Fox K. R. The GC-selective ligand mithramycin alters the structure of (AT)n sequences flanking its binding sites. FEBS Lett. 1990 May 7;264(1):100–104. doi: 10.1016/0014-5793(90)80775-e. [DOI] [PubMed] [Google Scholar]
  2. Fox K. R., Kentebe E. Echinomycin binding to the sequence CG(AT)nCG alters the structure of the central AT region. Nucleic Acids Res. 1990 Apr 25;18(8):1957–1963. doi: 10.1093/nar/18.8.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fox K. R., Kentebe E. Footprinting studies on the effect of echinomycin on the structure of a bent DNA fragment. Biochem J. 1990 Jul 1;269(1):217–221. doi: 10.1042/bj2690217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fox K. R., Wakelin L. P., Waring M. J. Kinetics of the interaction between echinomycin and deoxyribonucleic acid. Biochemistry. 1981 Sep 29;20(20):5768–5779. doi: 10.1021/bi00523a020. [DOI] [PubMed] [Google Scholar]
  5. Gao X. L., Patel D. J. NMR studies of echinomycin bisintercalation complexes with d(A1-C2-G3-T4) and d(T1-C2-G3-A4) duplexes in aqueous solution: sequence-dependent formation of Hoogsteen A1.T4 and Watson--Crick T1.A4 base pairs flanking the bisintercalation site. Biochemistry. 1988 Mar 8;27(5):1744–1751. doi: 10.1021/bi00405a054. [DOI] [PubMed] [Google Scholar]
  6. Krugh T. R. Association of actinomycin D and deoxyribodinucleotides as a model for binding of the drug to DNA. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1911–1914. doi: 10.1073/pnas.69.7.1911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Krugh T. R., Neely J. W. Actinomycin D-mononucleotide interactions as studied by proton magnetic resonance. Biochemistry. 1973 Apr 24;12(9):1775–1782. doi: 10.1021/bi00733a018. [DOI] [PubMed] [Google Scholar]
  8. Lee J. S., Waring M. J. Bifunctional intercalation and sequence specificity in the binding of quinomycin and triostin antibiotics to deoxyribonucleic acid. Biochem J. 1978 Jul 1;173(1):115–128. doi: 10.1042/bj1730115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lee J. S., Waring M. J. Interaction between synthetic analogues of quinoxaline antibiotics and nucleic acids. Changes in mechanism and specificity related to structural alterations. Biochem J. 1978 Jul 1;173(1):129–144. doi: 10.1042/bj1730129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Low C. M., Drew H. R., Waring M. J. Sequence-specific binding of echinomycin to DNA: evidence for conformational changes affecting flanking sequences. Nucleic Acids Res. 1984 Jun 25;12(12):4865–4879. doi: 10.1093/nar/12.12.4865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Low C. M., Fox K. R., Olsen R. K., Waring M. J. DNA sequence recognition by under-methylated analogues of triostin A. Nucleic Acids Res. 1986 Mar 11;14(5):2015–2033. doi: 10.1093/nar/14.5.2015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Low C. M., Olsen R. K., Waring M. J. Sequence preferences in the binding to DNA of triostin A and TANDEM as reported by DNase I footprinting. FEBS Lett. 1984 Oct 29;176(2):414–420. doi: 10.1016/0014-5793(84)81209-0. [DOI] [PubMed] [Google Scholar]
  13. Portugal J., Fox K. R., McLean M. J., Richenberg J. L., Waring M. J. Diethyl pyrocarbonate can detect a modified DNA structure induced by the binding of quinoxaline antibiotics. Nucleic Acids Res. 1988 May 11;16(9):3655–3670. doi: 10.1093/nar/16.9.3655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ughetto G., Wang A. H., Quigley G. J., van der Marel G. A., van Boom J. H., Rich A. A comparison of the structure of echinomycin and triostin A complexed to a DNA fragment. Nucleic Acids Res. 1985 Apr 11;13(7):2305–2323. doi: 10.1093/nar/13.7.2305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Van Dyke M. M., Dervan P. B. Echinomycin binding sites on DNA. Science. 1984 Sep 14;225(4667):1122–1127. doi: 10.1126/science.6089341. [DOI] [PubMed] [Google Scholar]
  16. Viswamitra M. A., Kennard O., Cruse W. B., Egert E., Sheldrick G. M., Jones P. G., Waring M. J., Wakelin L. P., Olsen R. K. Structure of TANDEM and its implication for bifunctional intercalation into DNA. Nature. 1981 Feb 26;289(5800):817–819. doi: 10.1038/289817a0. [DOI] [PubMed] [Google Scholar]
  17. Wakelin S. P., Waring M. J. The binding of echinomycin to deoxyribonucleic acid. Biochem J. 1976 Sep 1;157(3):721–740. doi: 10.1042/bj1570721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wang A. H., Ughetto G., Quigley G. J., Hakoshima T., van der Marel G. A., van Boom J. H., Rich A. The molecular structure of a DNA-triostin A complex. Science. 1984 Sep 14;225(4667):1115–1121. doi: 10.1126/science.6474168. [DOI] [PubMed] [Google Scholar]
  19. Waterloh K., Fox K. R. Effect of actinomycin on a (TA)6 plasmid insert. Anticancer Drug Des. 1990 Feb;5(1):89–92. [PubMed] [Google Scholar]
  20. Waterloh K., Fox K. R. The effects of actinomycin on the structure of dAn.dTn and (dA-dT)n regions surrounding its GC binding site. A footprinting study. J Biol Chem. 1991 Apr 5;266(10):6381–6388. [PubMed] [Google Scholar]

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