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. 1978 Dec;75(12):5983–5987. doi: 10.1073/pnas.75.12.5983

Interaction of bleomycin with DNA.

M Takeshita, A P Grollman, E Ohtsubo, H Ohtsubo
PMCID: PMC393101  PMID: 83650

Abstract

The sequence of oligonucleotides produced by the action of bleomycin and ferrous ion on double- and single-stranded DNA has been determined. In the presence of ferrous ion, bleomycin promotes cleavage at G-T and G-C sequences, while high concentrations of ferrous ion alone result in strand scission that is not base specific. In the presence of bleomycin and ferrous ion, pyrimidine bases located to the 3' side of guanosine are released preferentially and a low molecular weight product that forms a chromophore with thiobarbituric acid is produced from the deoxyribose moiety. Oligonucleotides produced by the action of bleomycin differ slightly in electrophoretic mobility from those produced by chemical or enzymatic cleavage. A model is proposed to explain the interactions of bleomycin with DNA.

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Selected References

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

  1. Dabrowiak J. C., Greenaway F. T., Longo W. E., Van Husen M., Crooke S. T. A spectroscopic investigation of the metal binding site of bleomycin A2. The Cu(II) and Zn(II) derivatives. Biochim Biophys Acta. 1978 Feb 16;517(2):517–526. doi: 10.1016/0005-2787(78)90218-6. [DOI] [PubMed] [Google Scholar]
  2. Godson G. N., Vapnek D. A simple method of preparing large amounts of phiX174 RF 1 supercoiled DNA. Biochim Biophys Acta. 1973 Apr 11;299(4):516–520. doi: 10.1016/0005-2787(73)90223-2. [DOI] [PubMed] [Google Scholar]
  3. Haidle C. W., Weiss K. K., Kuo M. T. Release of free bases from deoxyribonucleic acid after reaction with bleomycin. Mol Pharmacol. 1972 Sep;8(5):531–537. [PubMed] [Google Scholar]
  4. Hatayama T., Goldberg I. H., Takeshita M., Grollman A. P. Nucleotide specificity in DNA scission by neocarzinostatin. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3603–3607. doi: 10.1073/pnas.75.8.3603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ishida R., Takahashi T. Increased DNA chain breakage by combined action of bleomycin and superoxide radical. Biochem Biophys Res Commun. 1975 Oct 27;66(4):1432–1438. doi: 10.1016/0006-291x(75)90519-7. [DOI] [PubMed] [Google Scholar]
  6. Ishida R., Takahashi T. Increased DNA chain breakage by combined action of bleomycin and superoxide radical. Biochem Biophys Res Commun. 1975 Oct 27;66(4):1432–1438. doi: 10.1016/0006-291x(75)90519-7. [DOI] [PubMed] [Google Scholar]
  7. Ishizuka M., Takayama H., Takeuchi T., Umezawa H. Activity and toxicity of bleomycin. J Antibiot (Tokyo) 1967 Jan;20(1):15–24. [PubMed] [Google Scholar]
  8. Kappen L. S., Goldberg I. H. Gaps in DNA induced by neocarzinostatin bear 3'- and 5'-phosphoryl termini. Biochemistry. 1978 Feb 21;17(4):729–734. doi: 10.1021/bi00597a027. [DOI] [PubMed] [Google Scholar]
  9. Komano T., Sinsheimer R. L. Preparation and purification of phi X-RF component I. Biochim Biophys Acta. 1968 Jan 29;155(1):295–298. doi: 10.1016/0005-2787(68)90360-2. [DOI] [PubMed] [Google Scholar]
  10. Lown J. W., Sim S. K. The mechanism of the bleomycin-induced cleavage of DNA. Biochem Biophys Res Commun. 1977 Aug 22;77(4):1150–1157. doi: 10.1016/s0006-291x(77)80099-5. [DOI] [PubMed] [Google Scholar]
  11. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Müller W. E., Yamazaki Z., Breter H. J., Zahn R. K. Action of bleomycin on DNA and RNA. Eur J Biochem. 1972 Dec 18;31(3):518–525. doi: 10.1111/j.1432-1033.1972.tb02560.x. [DOI] [PubMed] [Google Scholar]
  13. Ohtsubo H., Ohtsubo E. Nucleotide sequence of an insertion element, IS1. Proc Natl Acad Sci U S A. 1978 Feb;75(2):615–619. doi: 10.1073/pnas.75.2.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Onishi T., Iwata H., Takagi Y. Effects of reducing and oxidizing agents on the action of bleomycin. J Biochem. 1975 Apr;77(4):745–752. doi: 10.1093/oxfordjournals.jbchem.a130778. [DOI] [PubMed] [Google Scholar]
  15. Sanger F., Air G. M., Barrell B. G., Brown N. L., Coulson A. R., Fiddes C. A., Hutchison C. A., Slocombe P. M., Smith M. Nucleotide sequence of bacteriophage phi X174 DNA. Nature. 1977 Feb 24;265(5596):687–695. doi: 10.1038/265687a0. [DOI] [PubMed] [Google Scholar]
  16. Sausville E. A., Peisach J., Horwitz S. B. A role for ferrous ion and oxygen in the degradation of DNA by bleomycin. Biochem Biophys Res Commun. 1976 Dec 6;73(3):814–822. doi: 10.1016/0006-291x(76)90882-2. [DOI] [PubMed] [Google Scholar]
  17. Sausville E. A., Peisach J., Horwitz S. B. Effect of chelating agents and metal ions on the degradation of DNA by bleomycin. Biochemistry. 1978 Jul 11;17(14):2740–2746. doi: 10.1021/bi00607a007. [DOI] [PubMed] [Google Scholar]
  18. Sausville E. A., Stein R. W., Peisach J., Horwitz S. B. Properties and products of the degradation of DNA by bleomycin and iron(II). Biochemistry. 1978 Jul 11;17(14):2746–2754. doi: 10.1021/bi00607a008. [DOI] [PubMed] [Google Scholar]
  19. Suzuki H., Nagai K., Yamaki H., Tanaka N., Umezawa H. On the mechanism of action of bleomycin: scission of DNA strands in vitro and in vivo. J Antibiot (Tokyo) 1969 Sep;22(9):446–448. doi: 10.7164/antibiotics.22.446. [DOI] [PubMed] [Google Scholar]
  20. Takeshita M., Grollman A. P., Horwitz S. B. Effect of ATP and other nucleotides on the bleomycin-induced degradation of vaccinia virus DNA. Virology. 1976 Feb;69(2):453–463. doi: 10.1016/0042-6822(76)90476-1. [DOI] [PubMed] [Google Scholar]
  21. Takeshita M., Horwitz S. B., Grollman A. P. Bleomycin, an inhibitor of vaccinia virus replication. Virology. 1974 Aug;60(2):455–465. doi: 10.1016/0042-6822(74)90339-0. [DOI] [PubMed] [Google Scholar]
  22. Tien Kuo M., Haidle C. W., Inners L. D. Characterization of bleomycin-resistant DNA. Biophys J. 1973 Dec;13(12):1296–1306. doi: 10.1016/s0006-3495(73)86063-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Umezawa H. Recent studies on bleomycin. Lloydia. 1977 Jan-Feb;40(1):67–81. [PubMed] [Google Scholar]
  24. ZAMENHOF S., GRIBOFF G., MARULLO N. Studies on the resistance of desoxyribonucleic acids to physical and chemical factors. Biochim Biophys Acta. 1954 Apr;13(4):459–470. doi: 10.1016/0006-3002(54)90362-5. [DOI] [PubMed] [Google Scholar]

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