TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication
- University of Dundee, United Kingdom
- 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
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.
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.
Metrics
-
- 3,219
- views
-
- 625
- downloads
-
- 71
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Citations by DOI
-
- 71
- citations for umbrella DOI https://doi.org/10.7554/eLife.48686
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
