Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1987 Oct 26;15(20):8217–8234. doi: 10.1093/nar/15.20.8217

Effects of the antitumor drug VP16 (etoposide) on the archaebacterial Halobacterium GRB 1.7 kb plasmid in vivo.

M Sioud 1, P Forterre 1, A M de Recondo 1
PMCID: PMC306355  PMID: 3671082

Abstract

The topoprofile of 1.7 kb plasmids from the archaebacterium Halobacterium GRB was analysed from cells growing with or without VP16 (etoposide). This drug interferes with the breakage-reunion reaction of eukaryotic DNA topoisomerase II by inhibiting the ligase activity of this enzyme. Addition of VP16 to the culture medium of Halobacterium GRB cells results in the introduction of single- and double-strand DNA breaks in part of the plasmid population, with proteins covalently associated at their 5' ends. While some of the remaining covalently closed circular DNA molecules are relaxed, VP16 treatment also gives rise to the production of positively supercoiled 1.7 kb plasmids. In contrast to adriamycin, VP16 does not intercalate into the 1.7 kb plasmid DNA in vivo. These results suggest that the VP16 target in halobacteria is a DNA topoisomerase II. Three major cleavage sites were detected on the 1.7 kb plasmid after VP16 treatment in vivo.

Full text

PDF
8217

Images in this article

Selected References

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

  1. 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]
  2. Cozzarelli N. R. DNA gyrase and the supercoiling of DNA. Science. 1980 Feb 29;207(4434):953–960. doi: 10.1126/science.6243420. [DOI] [PubMed] [Google Scholar]
  3. Forterre P., Mirambeau G., Jaxel C., Nadal M., Duguet M. High positive supercoiling in vitro catalyzed by an ATP and polyethylene glycol-stimulated topoisomerase from Sulfolobus acidocaldarius. EMBO J. 1985 Aug;4(8):2123–2128. doi: 10.1002/j.1460-2075.1985.tb03902.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gellert M. DNA topoisomerases. Annu Rev Biochem. 1981;50:879–910. doi: 10.1146/annurev.bi.50.070181.004311. [DOI] [PubMed] [Google Scholar]
  5. Gellert M., O'Dea M. H., Itoh T., Tomizawa J. Novobiocin and coumermycin inhibit DNA supercoiling catalyzed by DNA gyrase. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4474–4478. doi: 10.1073/pnas.73.12.4474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hsieh T., Brutlag D. ATP-dependent DNA topoisonmerase from D. melanogaster reversibly catenates duplex DNA rings. Cell. 1980 Aug;21(1):115–125. doi: 10.1016/0092-8674(80)90119-1. [DOI] [PubMed] [Google Scholar]
  7. Kikuchi A., Asai K. Reverse gyrase--a topoisomerase which introduces positive superhelical turns into DNA. Nature. 1984 Jun 21;309(5970):677–681. doi: 10.1038/309677a0. [DOI] [PubMed] [Google Scholar]
  8. Liu L. F. DNA topoisomerases--enzymes that catalyse the breaking and rejoining of DNA. CRC Crit Rev Biochem. 1983;15(1):1–24. doi: 10.3109/10409238309102799. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Lockshon D., Morris D. R. Positively supercoiled plasmid DNA is produced by treatment of Escherichia coli with DNA gyrase inhibitors. Nucleic Acids Res. 1983 May 25;11(10):2999–3017. doi: 10.1093/nar/11.10.2999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Long B. H., Musial S. T., Brattain M. G. Single- and double-strand DNA breakage and repair in human lung adenocarcinoma cells exposed to etoposide and teniposide. Cancer Res. 1985 Jul;45(7):3106–3112. [PubMed] [Google Scholar]
  12. Maxwell A., Gellert M. Mechanistic aspects of DNA topoisomerases. Adv Protein Chem. 1986;38:69–107. doi: 10.1016/s0065-3233(08)60526-4. [DOI] [PubMed] [Google Scholar]
  13. Mescher M. F., Strominger J. L. Purification and characterization of a prokaryotic glucoprotein from the cell envelope of Halobacterium salinarium. J Biol Chem. 1976 Apr 10;251(7):2005–2014. [PubMed] [Google Scholar]
  14. Mizuuchi K., O'Dea M. H., Gellert M. DNA gyrase: subunit structure and ATPase activity of the purified enzyme. Proc Natl Acad Sci U S A. 1978 Dec;75(12):5960–5963. doi: 10.1073/pnas.75.12.5960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pommier Y., Minford J. K., Schwartz R. E., Zwelling L. A., Kohn K. W. Effects of the DNA intercalators 4'-(9-acridinylamino)methanesulfon-m-anisidide and 2-methyl-9-hydroxyellipticinium on topoisomerase II mediated DNA strand cleavage and strand passage. Biochemistry. 1985 Nov 5;24(23):6410–6416. doi: 10.1021/bi00344a015. [DOI] [PubMed] [Google Scholar]
  16. Pommier Y., Schwartz R. E., Zwelling L. A., Kerrigan D., Mattern M. R., Charcosset J. Y., Jacquemin-Sablon A., Kohn K. W. Reduced formation of protein-associated DNA strand breaks in Chinese hamster cells resistant to topoisomerase II inhibitors. Cancer Res. 1986 Feb;46(2):611–616. [PubMed] [Google Scholar]
  17. Richter A., Strausfeld U., Knippers R. Effects of VM26 (teniposide), a specific inhibitor of type II DNA topoisomerase, on SV40 DNA replication in vivo. Nucleic Acids Res. 1987 Apr 24;15(8):3455–3468. doi: 10.1093/nar/15.8.3455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ross W., Rowe T., Glisson B., Yalowich J., Liu L. Role of topoisomerase II in mediating epipodophyllotoxin-induced DNA cleavage. Cancer Res. 1984 Dec;44(12 Pt 1):5857–5860. [PubMed] [Google Scholar]
  19. Rowe T. C., Wang J. C., Liu L. F. In vivo localization of DNA topoisomerase II cleavage sites on Drosophila heat shock chromatin. Mol Cell Biol. 1986 Apr;6(4):985–992. doi: 10.1128/mcb.6.4.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Snyder M., Drlica K. DNA gyrase on the bacterial chromosome: DNA cleavage induced by oxolinic acid. J Mol Biol. 1979 Jun 25;131(2):287–302. doi: 10.1016/0022-2836(79)90077-9. [DOI] [PubMed] [Google Scholar]
  21. Sugino A., Peebles C. L., Kreuzer K. N., Cozzarelli N. R. Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4767–4771. doi: 10.1073/pnas.74.11.4767. [DOI] [PMC free article] [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. Wang J. C. DNA topoisomerases. Annu Rev Biochem. 1985;54:665–697. doi: 10.1146/annurev.bi.54.070185.003313. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Zillig W., Schnabel R., Stetter K. O. Archaebacteria and the origin of the eukaryotic cytoplasm. Curr Top Microbiol Immunol. 1985;114:1–18. doi: 10.1007/978-3-642-70227-3_1. [DOI] [PubMed] [Google Scholar]

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

RESOURCES