IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms7572.html
   My bibliography  Save this article

TOPBP1 recruits TOP2A to ultra-fine anaphase bridges to aid in their resolution

Author

Listed:
  • Ronan Broderick

    (Weatherall Institute of Molecular Medicine, University of Oxford)

  • Jadwiga Nieminuszczy

    (Weatherall Institute of Molecular Medicine, University of Oxford
    Institute of Biochemistry and Biophysics, PAS)

  • Andrew N. Blackford

    (Weatherall Institute of Molecular Medicine, University of Oxford
    Present address: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK)

  • Alicja Winczura

    (Weatherall Institute of Molecular Medicine, University of Oxford
    Present address: Division of Biomedical Cell Biology, Warwick Medical School, The University of Warwick, Coventry CV4 7AL, UK)

  • Wojciech Niedzwiedz

    (Weatherall Institute of Molecular Medicine, University of Oxford)

Abstract

During mitosis, sister chromatids must be faithfully segregated to ensure that daughter cells receive one copy of each chromosome. However, following replication they often remain entangled. Topoisomerase IIα (TOP2A) has been proposed to resolve such entanglements, but the mechanisms governing TOP2A recruitment to these structures remain poorly understood. Here, we identify TOPBP1 as a novel interactor of TOP2A, and reveal that it is required for TOP2A recruitment to ultra-fine anaphase bridges (UFBs) in mitosis. The C-terminal region of TOPBP1 interacts with TOP2A, and TOPBP1 recruitment to UFBs requires its BRCT domain 5. Depletion of TOPBP1 leads to accumulation of UFBs, the majority of which arise from centromeric loci. Accordingly, expression of a TOPBP1 mutant that is defective in TOP2A binding phenocopies TOP2A depletion. These findings provide new mechanistic insights into how TOP2A promotes resolution of UFBs during mitosis, and highlights a pivotal role for TOPBP1 in this process.

Suggested Citation

  • Ronan Broderick & Jadwiga Nieminuszczy & Andrew N. Blackford & Alicja Winczura & Wojciech Niedzwiedz, 2015. "TOPBP1 recruits TOP2A to ultra-fine anaphase bridges to aid in their resolution," Nature Communications, Nature, vol. 6(1), pages 1-12, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7572
    DOI: 10.1038/ncomms7572
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms7572
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms7572?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
    ---><---

    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:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7572. 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.