TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication

  1. Remi Sonneville
  2. Rahul Bhowmick
  3. Saskia Hoffmann
  4. Niels mailand  Is a corresponding author
  5. Ian D Hickson  Is a corresponding author
  6. Karim Labib  Is a corresponding author
  1. University of Dundee, United Kingdom
  2. University of Copenhagen, Denmark

Abstract

The faithful segregation of eukaryotic chromosomes in mitosis requires that the genome be duplicated completely prior to anaphase. However, cells with large genomes sometimes fail to complete replication during interphase and instead enter mitosis with regions of incompletely replicated DNA. These regions are processed in early mitosis via a process known as mitotic DNA repair synthesis (MiDAS), but little is known about how cells switch from conventional DNA replication to MiDAS. Using the early embryo of the nematode Caenorhabditis elegans as a model system, we show that the TRAIP ubiquitin ligase drives replisome disassembly in response to incomplete DNA replication, thereby providing access to replication forks for other factors. Moreover, TRAIP is essential for MiDAS in human cells, and is important in both systems to prevent mitotic segregation errors. Our data indicate that TRAIP is a master regulator of the processing of incomplete DNA replication during mitosis in metazoa.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Remi Sonneville

    MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Rahul Bhowmick

    Center for Chromosome Stability, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  3. Saskia Hoffmann

    Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  4. Niels mailand

    Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    For correspondence
    niels.mailand@cpr.ku.dk
    Competing interests
    The authors declare that no competing interests exist.
  5. Ian D Hickson

    Center for Chromosome Stability, University of Copenhagen, Copenhagen, Denmark
    For correspondence
    iandh@sund.ku.dk
    Competing interests
    The authors declare that no competing interests exist.
  6. Karim Labib

    MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, United Kingdom
    For correspondence
    kpmlabib@dundee.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8861-379X

Funding

Medical Research Council (MC_UU_12016/13)

  • Remi Sonneville
  • Karim Labib

Cancer Research UK (C578/A24558)

  • Remi Sonneville
  • Karim Labib

Wellcome (102943/Z/13/Z)

  • Karim Labib

Danish National Research Foundation (DNRF115)

  • Ian D Hickson

Danish Medical Research Council (DFF-4004-00155B)

  • Rahul Bhowmick

H2020 European Research Council (616236)

  • Niels mailand

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Andrés Aguilera, CABIMER, Universidad de Sevilla, Spain

Publication history

  1. Received: May 22, 2019
  2. Accepted: September 20, 2019
  3. Accepted Manuscript published: September 23, 2019 (version 1)
  4. Version of Record published: October 1, 2019 (version 2)

Copyright

© 2019, Sonneville et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Remi Sonneville
  2. Rahul Bhowmick
  3. Saskia Hoffmann
  4. Niels mailand
  5. Ian D Hickson
  6. Karim Labib
(2019)
TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication
eLife 8:e48686.
https://doi.org/10.7554/eLife.48686

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