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

Remi Sonneville, Rahul Bhowmick, Saskia Hoffmann, Niels Mailand, Ian D. Hickson (Lead / Corresponding author), Karim Labib (Lead / Corresponding author)

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number48686
Pages (from-to)1-19
Number of pages19
JournaleLife
Volume8
DOIs
Publication statusPublished - 23 Sep 2019

Fingerprint

DNA Replication
Mitosis
DNA Repair
Repair
DNA
Genome
Chromosome Segregation
Anaphase
Interphase
Caenorhabditis elegans
Ligases
Ubiquitin
Genes
Embryonic Structures
Chromosomes
Cells
Switches
Processing

Cite this

Sonneville, Remi ; Bhowmick, Rahul ; Hoffmann, Saskia ; Mailand, Niels ; Hickson, Ian D. ; Labib, Karim. / TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication. In: eLife. 2019 ; Vol. 8. pp. 1-19.
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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.",
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TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication. / Sonneville, Remi; Bhowmick, Rahul; Hoffmann, Saskia; Mailand, Niels; Hickson, Ian D. (Lead / Corresponding author); Labib, Karim (Lead / Corresponding author).

In: eLife, Vol. 8, 48686, 23.09.2019, p. 1-19.

Research output: Contribution to journalArticle

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