IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v525y2015i7569d10.1038_nature14887.html
   My bibliography  Save this article

The mechanism of DNA replication termination in vertebrates

Author

Listed:
  • James M. Dewar

    (Harvard Medical School)

  • Magda Budzowska

    (Harvard Medical School)

  • Johannes C. Walter

    (Harvard Medical School
    Howard Hughes Medical Institute, Harvard Medical School)

Abstract

Eukaryotic DNA replication terminates when replisomes from adjacent replication origins converge. Termination involves local completion of DNA synthesis, decatenation of daughter molecules and replisome disassembly. Termination has been difficult to study because termination events are generally asynchronous and sequence nonspecific. To overcome these challenges, we paused converging replisomes with a site-specific barrier in Xenopus egg extracts. Upon removal of the barrier, forks underwent synchronous and site-specific termination, allowing mechanistic dissection of this process. We show that DNA synthesis does not slow detectably as forks approach each other, and that leading strands pass each other unhindered before undergoing ligation to downstream lagging strands. Dissociation of the replicative CMG helicase (comprising CDC45, MCM2-7 and GINS) occurs only after the final ligation step, and is not required for completion of DNA synthesis, strongly suggesting that converging CMGs pass one another and dissociate from double-stranded DNA. This termination mechanism allows rapid completion of DNA synthesis while avoiding premature replisome disassembly.

Suggested Citation

  • James M. Dewar & Magda Budzowska & Johannes C. Walter, 2015. "The mechanism of DNA replication termination in vertebrates," Nature, Nature, vol. 525(7569), pages 345-350, September.
    • Handle: RePEc:nat:nature:v:525:y:2015:i:7569:d:10.1038_nature14887
    DOI: 10.1038/nature14887
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature14887
    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/nature14887?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. Hana Polasek-Sedlackova & Thomas C. R. Miller & Jana Krejci & Maj-Britt Rask & Jiri Lukas, 2022. "Solving the MCM paradox by visualizing the scaffold of CMG helicase at active replisomes," Nature Communications, Nature, vol. 13(1), pages 1-11, 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:525:y:2015:i:7569:d:10.1038_nature14887. 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.