Skip to main content
SpringerLink
Log in

Topoisomerases — from Basic Research to Clinical Implications

  • Conference paper
Acute Leukemias V

Part of the book series: Haematology and Blood Transfusion / Hämatologie und Bluttransfusion ((HAEMATOLOGY,volume 37))

  • 73 Accesses

Abstract

Topoisomerases (topos) are moved into the focus of haematologists and oncologists because they are interesting in several different aspects. These enzymes are life-important DNA-processing enzymes, their activity is necessary in every cellular action where alteration of the three-dimensional structure of the DNA is obligatory. Moreover, research on topos has a direct clinical aspect because topo I as well as topo II are target structures for several important cytostatics. In the following paper I will focus on the clinical part of this research area and will cover just the basic facts which are necessary to understand the clinical importance of these enzymes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Uemura T, Ohkura H, Adachi Y, Morino K, Shiozaki K, Yanagida M. DNA topoisomerase II is required for condensation and separation of mitotic chromosomes in S. pombe. Cell 1987; 50: 917–925.

    Article  PubMed  CAS  Google Scholar 

  2. Tsao Y, Wu H, Liu LF. Transcription-driven supercoiling of DNA: direct biochemical evidence from in vitro studies. Cell 1989;56: 111–118.

    Article  PubMed  CAS  Google Scholar 

  3. Menzel R, Gellert M. Regulation of the genes for E. coli DNA gyrase: homeostatic control of DNA supercoiling. Cell 1983;34: 105–113.

    Article  PubMed  CAS  Google Scholar 

  4. Tan KB, Dorman TE, Falls KM, et al. Topoisomerase IIa and Topoisomerase IIβ Genes: Characterization and Mapping to Human Chromosomes 17 and 3, Respectively. Cancer Research 1992; 52: 231–234.

    PubMed  CAS  Google Scholar 

  5. Takano H, Kohno K, Ono M, Uchida Y, Kuwano M. Increased Phosphorylation of DNA Topoisomerase II in Etoposide-resistant Mutants of Human Cancer KB Cells. Cancer Research 1991;51: 3951–3957.

    PubMed  CAS  Google Scholar 

  6. Samuels DS, Shimizu N. DNA topoisomerase I phosphorylation in murine fibroblasts treated with 12-O-tetradecanoylphorbol-13-acetate and in vitro by protein kinase. J Biol Chem 1992;267(16): 11156–62.

    PubMed  CAS  Google Scholar 

  7. Schroder HC, Steffen R, Wenger R, Ugarkovic D, Muller WE. Age-dependent increase of DNA topoisomerase II activity in quail oviduct; modulation of the nuclear matrix-associated enzyme activity by protein phosphorylation and poly(ADP-ribosyl)ation. Mutat Res 1989;219(5–6): 283–94.

    PubMed  CAS  Google Scholar 

  8. Gasser SM, Walter R, Dang Q, Cardenas ME. Topoisomerase II: its functions and phosphorylation. Antonie Van Leeuwenhoek 1992;62(1–2): 15–24.

    Article  PubMed  CAS  Google Scholar 

  9. Heck MM, Hittelman WN, Earnshaw WC. In vivo phosphorylation of the 170-kDa form of eukaryotic DNA topoisomerase II. Cell cycle analysis. J Biol Chem 1989;264(26): 15161–4.

    PubMed  CAS  Google Scholar 

  10. Osheroff N. Eukaryotic topoisomerase II. J. Biol. Chem. 1986;261: 9944–9950.

    PubMed  CAS  Google Scholar 

  11. Gieseler F, Boege F, Ruf B, Meyer P, Wilms K. Molecular pathways of topoisomerase II regulation and consequences for chemotherapy. In Hiddemann W. et al.: Leukemia IV, Springer Verlag 1993;in press.

    Google Scholar 

  12. Earnshaw WC, Halligen B, Cooke CA, Heck MM, Liu LF. Topoisomerase II is a structural component of mitoic chromosome scaffolds. J. Cell. Biol. 1985;100: 1706–1715.

    Article  PubMed  CAS  Google Scholar 

  13. Tsutsui K, Tsutsui K, Muller MT. The nuclear scaffold exhibites DNA-binding sites selective for supercoiled DNA. J. Biol. Chem. 1988;263: 7235–7241.

    PubMed  CAS  Google Scholar 

  14. Laemmli UK, Gasser SM. A glimpse at chromosomal order. Trends in Genetics 1987;3.

    Google Scholar 

  15. Boege F, Kjeldsen E, Gieseler F, Alsner J, Biersack H. A drug-resistant variant of topoisomerase II alpha in human HL-60 cells exhibits alterations in catalytic pH optimum, DNA binding and sub-nuclear distribution. Eur. J. Biochem. 1993;218: 575–584.

    Article  PubMed  CAS  Google Scholar 

  16. Zwelling LA, Chan D, Hinds M, Mayes J, Silberman LE, Blick M. Effect of phorbol ester treatment on drug-induced, topoisomerase II-mediated DNA cleavage in human leukemia cells. Cancer Res 1988;48(23): 6625–33.

    PubMed  CAS  Google Scholar 

  17. Gieseler F, Boege F, Clark M. Alteration of topoisomerase II action is a possible mechanism of HL-60 cell differentiation. Environ Health Persp 1990; 88: 183–185.

    Article  CAS  Google Scholar 

  18. Gieseler F, Boege F, Biersack H, Spohn B, Clark M, Wilms K. Nuclear topisomerase II activity changes during HL-60 cell differentiation: alterations of drug sensitivity and pH-dependency. Leukemia and Lymphoma 1991; 5: 273–279.

    Article  Google Scholar 

  19. Nishiyama M, Horichi N, Mazouzi Z, Bungo M, Saijo N, Tapiero H. Can cytotoxic activity of anthracyclines be related to DNA damage? Anticancer Drug Des 1990;5(1): 135–9.

    PubMed  CAS  Google Scholar 

  20. Belvedere G, Suarato A, Geroni C, Giuliani FC, D’Incalci M. Comparison of intracellular drug retention, DNA damage and cytotoxicity of derivatives of doxorubicin and daunorubicin in a human colon adenocarcinoma cell line (LoVo). Biochem Pharmacol 1989;38(21): 3713–21.

    Article  PubMed  CAS  Google Scholar 

  21. Zunino F, Capranico G. DNA topoisomerase II as the primary target of antitumor anthracyclines. Anticancer Drug Des 1990;5(4): 307–17.

    PubMed  CAS  Google Scholar 

  22. Gieseler F, Boege F, Biersack H, Mühlen I, Meyer P. Correlation between the DNA-binding affinity of anthracyclines and their cytotoxicity in vitro. Proc. Fourth Internatl. Congress on Anti-Cancer Chemotherapy. Paris, France 1993;: Abstr.169.

    Google Scholar 

  23. Gieseler F, Biersack H, Brieden T, Manderscheid J, Nüßler V. Cytotoxicity of anthracyclines: correlation with cellular uptake, intracellular distribution and DNA-binding. Ann. Haematol. 1994;Supported.

    Google Scholar 

  24. Capranico G, Riva A, Tinalli S, Dasdia T, Zunino F. Markedly reduced levels of anthracycline-induced DNA strand breaks in resistant P388 leukemia cells and isolated nuclei. Cancer Res. 1987;47: 3752–3756.

    PubMed  CAS  Google Scholar 

  25. Sorensen BS, Sinding J, Andersen AH, Alsner J, Jensen PB, Westergaard O. Mode of action of topoisomerase II-targeting agents at a specific DNA sequence. Uncoupling the DNA binding, cleavage and religation events. J Mol Biol 1992;228(3): 778–86.

    Article  PubMed  CAS  Google Scholar 

  26. Robinson MJ, Corbett AH, Osheroff N. Effects of topoisomerase II-targeted drugs on enzyme-mediated DNA cleavage and ATP hydrolysis: evidence for distinct drug interaction domains on topoisomerase II. Biochemistry 1993;32(14): 3638–43.

    Article  PubMed  CAS  Google Scholar 

  27. Jensen PB, Sorensen BS, Demant EJ, et al. Antagonistic effect of aclarubicin on the cytotoxicity of etoposide and 4′-(9-acridinylamino) methanesulfon-m-anisidide in human small cell lung cancer cell lines and on topoisomerase II-mediated DNA cleavage. Cancer Res 1990;50(11): 3311–6.

    PubMed  CAS  Google Scholar 

  28. Jensen PB, Jensen PS, Demant EJ et al. Antagonistic effect of aclarubicin on daunorubicin-induced cytotoxicity in human small cell lung cancer cells: relationship to DNA integrity and topoisomerase II. Cancer Res I991;51(19): 5093–9.

    PubMed  CAS  Google Scholar 

  29. Erttmann R, Boetefür A, Erttmann KD, Gieseler F, Looft G. Conserved cytotoxic activity of aclacinomycin A in multifactorial multidrug resistance. Haematology and Blood Transfusion 1992;34: 49–55.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Poliklinik, University Hospital, 97070, Würzburg, Germany

    Frank Gieseler

Authors
  1. Frank Gieseler
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Internal Medicine, University of Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany

    W. Hiddemann  & W. Plunkett  & 

  2. Department of Internal Medicine, University of Münster, Albert-Schweitzer-Strasse 33, 48145, Münster, Germany

    T. Büchner

  3. Department of Pediatric Oncology, University of Münster, Albert-Schweitzer-Strasse 33, 48145, Münster, Germany

    J. Ritter

  4. Department of Internal Medicine, MD Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA

    B. Wörmann M.D., Ph.D.  & M. J. Keating M.D., B.S.  & 

  5. Koordinierungsstelle, Deutsche Krebsgesellschaft e.V., Thea-Bähnisch-Weg 12, 30657, Hannover, Germany

    U. Creutzig

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Gieseler, F. (1996). Topoisomerases — from Basic Research to Clinical Implications. In: Hiddemann, W., et al. Acute Leukemias V. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78907-6_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-78907-6_13

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-78909-0

  • Online ISBN: 978-3-642-78907-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation