Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Jun;79(11):3489–3492. doi: 10.1073/pnas.79.11.3489

Ethidium bromide changes the nuclease-sensitive DNA binding sites of the antitumor drug cis-diamminedichloroplatinum(II).

T D Tullius, S J Lippard
PMCID: PMC346446  PMID: 6954494

Abstract

Exonuclease III has been shown previously to reveal the binding sites of the antitumor drug cis-diamminedichloroplatinum(II) on DNA. Pretreatment of the same DNA with the intercalator ethidium bromide causes new platinum binding sites to be detected by the exonuclease III method. In particular, a 5'd(G6-D-G2)3' sequence in a 165-base-pair restriction fragment of plasmid pBR322 becomes a preferred site for exonuclease III-detectable cis-diamminedichloroplatinum(II)binding. This switching of nuclease-sensitive platinum binding to new sites by the influence of another drug, ethidium bromide, offers an explantation at the molecular level for the phenomenon of synergism in combination chemotherapy.

Full text

PDF
3489

Images in this article

3490Image
on p.3490
3491Image
on p.3491
3492Image
on p.3492

Selected References

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

  1. Bresloff J. L., Crothers D. M. Equilibrium studies of ethidium--polynucleotide interactions. Biochemistry. 1981 Jun 9;20(12):3547–3553. doi: 10.1021/bi00515a038. [DOI] [PubMed] [Google Scholar]
  2. Dickerson R. E., Drew H. R. Structure of a B-DNA dodecamer. II. Influence of base sequence on helix structure. J Mol Biol. 1981 Jul 15;149(4):761–786. doi: 10.1016/0022-2836(81)90357-0. [DOI] [PubMed] [Google Scholar]
  3. Dingwall C., Lomonossoff G. P., Laskey R. A. High sequence specificity of micrococcal nuclease. Nucleic Acids Res. 1981 Jun 25;9(12):2659–2673. doi: 10.1093/nar/9.12.2659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hörz W., Altenburger W. Sequence specific cleavage of DNA by micrococcal nuclease. Nucleic Acids Res. 1981 Jun 25;9(12):2643–2658. doi: 10.1093/nar/9.12.2643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Lomonossoff G. P., Butler P. J., Klug A. Sequence-dependent variation in the conformation of DNA. J Mol Biol. 1981 Jul 15;149(4):745–760. doi: 10.1016/0022-2836(81)90356-9. [DOI] [PubMed] [Google Scholar]
  6. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  7. Roberts J. J., Thomson A. J. The mechanism of action of antitumor platinum compounds. Prog Nucleic Acid Res Mol Biol. 1979;22:71–133. doi: 10.1016/s0079-6603(08)60799-0. [DOI] [PubMed] [Google Scholar]
  8. Rogers S. G., Weiss B. Exonuclease III of Escherichia coli K-12, an AP endonuclease. Methods Enzymol. 1980;65(1):201–211. doi: 10.1016/s0076-6879(80)65028-9. [DOI] [PubMed] [Google Scholar]
  9. Royer-Pokora B., Gordon L. K., Haseltine W. A. Use of exonuclease III to determine the site of stable lesions in defined sequences of DNA: the cyclobutane pyrimidine dimer and cis and trans dichlorodiammine platinum II examples. Nucleic Acids Res. 1981 Sep 25;9(18):4595–4609. doi: 10.1093/nar/9.18.4595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Sanger F., Coulson A. R. The use of thin acrylamide gels for DNA sequencing. FEBS Lett. 1978 Mar 1;87(1):107–110. doi: 10.1016/0014-5793(78)80145-8. [DOI] [PubMed] [Google Scholar]
  11. Stone P. J., Kelman A. D., Sinex F. M. Resolution of alpha, beta and gamma DNA of Saccharomyces cerevisiae with the antitumor drug cis-Pt (NH3)2CL2. Evidence for preferential drug binding by GpG sequences of DNA. J Mol Biol. 1976 Jul 15;104(4):793–801. doi: 10.1016/0022-2836(76)90182-0. [DOI] [PubMed] [Google Scholar]
  12. Stone P. J., Kelman A. D., Sinex F. M. Specific binding of antitumour drug cis-Pt(NH3)2C12 to DNA rich in guanine and cytosine. Nature. 1974 Oct 25;251(5477):736–737. doi: 10.1038/251736a0. [DOI] [PubMed] [Google Scholar]
  13. Sutcliffe J. G. Complete nucleotide sequence of the Escherichia coli plasmid pBR322. Cold Spring Harb Symp Quant Biol. 1979;43(Pt 1):77–90. doi: 10.1101/sqb.1979.043.01.013. [DOI] [PubMed] [Google Scholar]
  14. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES