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.
All data generated or analysed during this study are included in the manuscript and supporting files.
- Remi Sonneville
- Karim Labib
- Remi Sonneville
- Karim Labib
- Karim Labib
- Ian D Hickson
- Rahul Bhowmick
- Niels mailand
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Andrés Aguilera, CABIMER, Universidad de Sevilla, Spain
© 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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