IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v411y2001i6841d10.1038_35082600.html
   My bibliography  Save this article

Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms

Author

Listed:
  • Van Q. Nguyen

    (Department of Biochemistry and Biophysics)

  • Carl Co

    (Department of Biochemistry and Biophysics)

  • Joachim J. Li

    (University of California)

Abstract

The stable propagation of genetic information requires that the entire genome of an organism be faithfully replicated once and only once each cell cycle. In eukaryotes, this replication is initiated at hundreds to thousands of replication origins distributed over the genome, each of which must be prohibited from re-initiating DNA replication within every cell cycle. How cells prevent re-initiation has been a long-standing question in cell biology. In several eukaryotes, cyclin-dependent kinases (CDKs) have been implicated in promoting the block to re-initiation1, but exactly how they perform this function is unclear. Here we show that B-type CDKs in Saccharomyces cerevisiae prevent re-initiation through multiple overlapping mechanisms, including phosphorylation of the origin recognition complex (ORC), downregulation of Cdc6 activity, and nuclear exclusion of the Mcm2-7 complex. Only when all three inhibitory pathways are disrupted do origins re-initiate DNA replication in G2/M cells. These studies show that each of these three independent mechanisms of regulation is functionally important.

Suggested Citation

  • Van Q. Nguyen & Carl Co & Joachim J. Li, 2001. "Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms," Nature, Nature, vol. 411(6841), pages 1068-1073, June.
    • Handle: RePEc:nat:nature:v:411:y:2001:i:6841:d:10.1038_35082600
    DOI: 10.1038/35082600
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/35082600
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/35082600?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.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Aftab Amin & Cheung Man Hei & Chun Liang & Aftab Amin & Cheung Man Hei & Chun Liang & Chun Liang & Aftab Amin & Cheung Man Hei & Chun Liang, 2019. "DNA Replication-Initiation Proteins in Eukaryotic Cells," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 22(5), pages 17042-17049, December.
    2. Jan Marten Schmidt & Ran Yang & Ashish Kumar & Olivia Hunker & Jan Seebacher & Franziska Bleichert, 2022. "A mechanism of origin licensing control through autoinhibition of S. cerevisiae ORC·DNA·Cdc6," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Yue Wu & Qiongdan Zhang & Yuhan Lin & Wai Hei Lam & Yuanliang Zhai, 2024. "Replication licensing regulated by a short linear motif within an intrinsically disordered region of origin recognition complex," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. Anneke Brümmer & Carlos Salazar & Vittoria Zinzalla & Lilia Alberghina & Thomas Höfer, 2010. "Mathematical Modelling of DNA Replication Reveals a Trade-off between Coherence of Origin Activation and Robustness against Rereplication," PLOS Computational Biology, Public Library of Science, vol. 6(5), pages 1-13, May.
    5. Karl-Uwe Reusswig & Julia Bittmann & Martina Peritore & Mathilde Courtes & Benjamin Pardo & Michael Wierer & Matthias Mann & Boris Pfander, 2022. "Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

    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:411:y:2001:i:6841:d:10.1038_35082600. 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.