IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v448y2007i7150d10.1038_nature05938.html
   My bibliography  Save this article

Antitumour drugs impede DNA uncoiling by topoisomerase I

Author

Listed:
  • Daniel A. Koster

    (Kavli Institute of Nanoscience, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands)

  • Komaraiah Palle

    (St Jude Children’s Research Hospital, 332 N. Lauderdale, Memphis, Tennessee 38105, USA)

  • Elisa S. M. Bot

    (Kavli Institute of Nanoscience, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands)

  • Mary-Ann Bjornsti

    (St Jude Children’s Research Hospital, 332 N. Lauderdale, Memphis, Tennessee 38105, USA)

  • Nynke H. Dekker

    (Kavli Institute of Nanoscience, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands)

Abstract

Supercoiled Topoisomerases are enzymes that act to relax supercoiling, a form of built-up strain in DNA. Topoisomerase inhibitors are important antitumour drugs, thought to act by stabilizing a covalent complex between the topoisomerase and DNA, which then sets up a road-block to the DNA replication machinery. The origin of drug efficacy in targeting topoisomerases remains poorly understood, but now a singlemolecule study of the interaction of topotecan, a drug used mainly to treat ovarian cancer and small-cell lung cancer, and a topoisomerase IB–DNA complex, has revealed more details of the process. As illustrated on the cover, positive DNA supercoils accumulate due to the action of the drug (shown red) Such overwinding of the DNA hinders an advancing DNA polymerase and may play a role in the stalling or collapse of a replication fork, ultimately leading to cell death.

Suggested Citation

  • Daniel A. Koster & Komaraiah Palle & Elisa S. M. Bot & Mary-Ann Bjornsti & Nynke H. Dekker, 2007. "Antitumour drugs impede DNA uncoiling by topoisomerase I," Nature, Nature, vol. 448(7150), pages 213-217, July.
    • Handle: RePEc:nat:nature:v:448:y:2007:i:7150:d:10.1038_nature05938
    DOI: 10.1038/nature05938
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature05938
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature05938?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:448:y:2007:i:7150:d:10.1038_nature05938. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.