Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1991 Jun 11;19(11):2861–2868. doi: 10.1093/nar/19.11.2861

Sequence requirements for mammalian topoisomerase II mediated DNA cleavage stimulated by an ellipticine derivative.

P Fossé 1, B René 1, M Le Bret 1, C Paoletti 1, J M Saucier 1
PMCID: PMC328243  PMID: 1647520

Abstract

Various antitumor drugs stabilize DNA topoisomerase II-DNA transient covalent complexes. The complexes distribution along pBR322 DNA was shown previously to depend upon the nature of the drug (Tewey et al. (1984) Science 226, 466-468). The position in pBR322 of DNA cleavage by calf DNA topoisomerase II for 115 such sites stabilized by an ellipticine derivative and the relative frequency of cleavage at most of these sites were determined. The nucleotide sequence surrounding the 25 strongest sites was analyzed and the following ellipticine specific consensus sequence was deduced: 5'-ANCNT(A/G)T.NN(G/C)N(A/G)-3' where cleavage occurs at the indicated mark. A thymine is always present at the 3' end of at least one strand of the strong cleavage sites, and the dinucleotide AT or GT at the 3' end of the break plays a major role in the complex stabilisation. The predictive value of cleavage of the consensus was tested for two regions of SV40 DNA and cleavage was indeed detected at the majority of the sites matching the consensus. Some complexes stabilized by ellipticine are resistant to salt dissociation and this property seems to be correlated with the presence of symmetrical sequences in the cleavage site with a center of symmetry staggered relatively to the center of symmetry of cleavage.

Full text

PDF
2861

Images in this article

2862Image
on p.2862
2863Image
on p.2863
2864Image
on p.2864
2866Image
on p.2866

Selected References

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

  1. Capranico G., Kohn K. W., Pommier Y. Local sequence requirements for DNA cleavage by mammalian topoisomerase II in the presence of doxorubicin. Nucleic Acids Res. 1990 Nov 25;18(22):6611–6619. doi: 10.1093/nar/18.22.6611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chen G. L., Yang L., Rowe T. C., Halligan B. D., Tewey K. M., Liu L. F. Nonintercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II. J Biol Chem. 1984 Nov 10;259(21):13560–13566. [PubMed] [Google Scholar]
  3. D'Arpa P., Liu L. F. Topoisomerase-targeting antitumor drugs. Biochim Biophys Acta. 1989 Dec 17;989(2):163–177. doi: 10.1016/0304-419x(89)90041-3. [DOI] [PubMed] [Google Scholar]
  4. Darby M. K., Herrera R. E., Vosberg H. P., Nordheim A. DNA topoisomerase II cleaves at specific sites in the 5' flanking region of c-fos proto-oncogenes in vitro. EMBO J. 1986 Sep;5(9):2257–2265. doi: 10.1002/j.1460-2075.1986.tb04493.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Halligan B. D., Edwards K. A., Liu L. F. Purification and characterization of a type II DNA topoisomerase from bovine calf thymus. J Biol Chem. 1985 Feb 25;260(4):2475–2482. [PubMed] [Google Scholar]
  6. Kohn K. W., Pommier Y., Kerrigan D., Markovits J., Covey J. M. Topoisomerase II as a target of anticancer drug action in mammalian cells. NCI Monogr. 1987;(4):61–71. [PubMed] [Google Scholar]
  7. Lee M. P., Sander M., Hsieh T. Nuclease protection by Drosophila DNA topoisomerase II. Enzyme/DNA contacts at the strong topoisomerase II cleavage sites. J Biol Chem. 1989 Dec 25;264(36):21779–21787. [PubMed] [Google Scholar]
  8. Liu L. F., Rowe T. C., Yang L., Tewey K. M., Chen G. L. Cleavage of DNA by mammalian DNA topoisomerase II. J Biol Chem. 1983 Dec 25;258(24):15365–15370. [PubMed] [Google Scholar]
  9. Lund K., Andersen A. H., Christiansen K., Svejstrup J. Q., Westergaard O. Minimal DNA requirement for topoisomerase II-mediated cleavage in vitro. J Biol Chem. 1990 Aug 15;265(23):13856–13863. [PubMed] [Google Scholar]
  10. Markovits J., Linassier C., Fossé P., Couprie J., Pierre J., Jacquemin-Sablon A., Saucier J. M., Le Pecq J. B., Larsen A. K. Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II. Cancer Res. 1989 Sep 15;49(18):5111–5117. [PubMed] [Google Scholar]
  11. 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]
  12. Miller K. G., Liu L. F., Englund P. T. A homogeneous type II DNA topoisomerase from HeLa cell nuclei. J Biol Chem. 1981 Sep 10;256(17):9334–9339. [PubMed] [Google Scholar]
  13. Osheroff N. Effect of antineoplastic agents on the DNA cleavage/religation reaction of eukaryotic topoisomerase II: inhibition of DNA religation by etoposide. Biochemistry. 1989 Jul 25;28(15):6157–6160. doi: 10.1021/bi00441a005. [DOI] [PubMed] [Google Scholar]
  14. Peden K. W. Revised sequence of the tetracycline-resistance gene of pBR322. Gene. 1983 May-Jun;22(2-3):277–280. doi: 10.1016/0378-1119(83)90112-9. [DOI] [PubMed] [Google Scholar]
  15. Rowe T. C., Chen G. L., Hsiang Y. H., Liu L. F. DNA damage by antitumor acridines mediated by mammalian DNA topoisomerase II. Cancer Res. 1986 Apr;46(4 Pt 2):2021–2026. [PubMed] [Google Scholar]
  16. Sander M., Hsieh T. S. Drosophila topoisomerase II double-strand DNA cleavage: analysis of DNA sequence homology at the cleavage site. Nucleic Acids Res. 1985 Feb 25;13(4):1057–1072. doi: 10.1093/nar/13.4.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sander M., Hsieh T. Double strand DNA cleavage by type II DNA topoisomerase from Drosophila melanogaster. J Biol Chem. 1983 Jul 10;258(13):8421–8428. [PubMed] [Google Scholar]
  18. Schneider T. D., Stormo G. D., Gold L., Ehrenfeucht A. Information content of binding sites on nucleotide sequences. J Mol Biol. 1986 Apr 5;188(3):415–431. doi: 10.1016/0022-2836(86)90165-8. [DOI] [PubMed] [Google Scholar]
  19. Sperry A. O., Blasquez V. C., Garrard W. T. Dysfunction of chromosomal loop attachment sites: illegitimate recombination linked to matrix association regions and topoisomerase II. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5497–5501. doi: 10.1073/pnas.86.14.5497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Spitzner J. R., Muller M. T. A consensus sequence for cleavage by vertebrate DNA topoisomerase II. Nucleic Acids Res. 1988 Jun 24;16(12):5533–5556. doi: 10.1093/nar/16.12.5533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sørensen B. S., Jensen P. S., Andersen A. H., Christiansen K., Alsner J., Thomsen B., Westergaard O. Stimulation of topoisomerase II mediated DNA cleavage at specific sequence elements by the 2-nitroimidazole Ro 15-0216. Biochemistry. 1990 Oct 16;29(41):9507–9515. doi: 10.1021/bi00493a003. [DOI] [PubMed] [Google Scholar]
  22. Tewey K. M., Chen G. L., Nelson E. M., Liu L. F. Intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II. J Biol Chem. 1984 Jul 25;259(14):9182–9187. [PubMed] [Google Scholar]
  23. Tewey K. M., Rowe T. C., Yang L., Halligan B. D., Liu L. F. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science. 1984 Oct 26;226(4673):466–468. doi: 10.1126/science.6093249. [DOI] [PubMed] [Google Scholar]
  24. Thomsen B., Bendixen C., Lund K., Andersen A. H., Sørensen B. S., Westergaard O. Characterization of the interaction between topoisomerase II and DNA by transcriptional footprinting. J Mol Biol. 1990 Sep 20;215(2):237–244. doi: 10.1016/S0022-2836(05)80342-0. [DOI] [PubMed] [Google Scholar]
  25. Wang J. C. DNA topoisomerases. Annu Rev Biochem. 1985;54:665–697. doi: 10.1146/annurev.bi.54.070185.003313. [DOI] [PubMed] [Google Scholar]
  26. Yang L., Rowe T. C., Liu L. F. Identification of DNA topoisomerase II as an intracellular target of antitumor epipodophyllotoxins in simian virus 40-infected monkey cells. Cancer Res. 1985 Nov;45(11 Pt 2):5872–5876. [PubMed] [Google Scholar]
  27. Yang L., Rowe T. C., Nelson E. M., Liu L. F. In vivo mapping of DNA topoisomerase II-specific cleavage sites on SV40 chromatin. Cell. 1985 May;41(1):127–132. doi: 10.1016/0092-8674(85)90067-4. [DOI] [PubMed] [Google Scholar]
  28. Zwelling L. A., Michaels S., Kerrigan D., Pommier Y., Kohn K. W. Protein-associated deoxyribonucleic acid strand breaks produced in mouse leukemia L1210 cells by ellipticine and 2-methyl-9-hydroxyellipticinium. Biochem Pharmacol. 1982 Oct 15;31(20):3261–3267. doi: 10.1016/0006-2952(82)90560-3. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES