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; Karim Labib

doi:10.7554/eLife.48686

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)

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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 language	English
Article number	e48686
Pages (from-to)	1-19
Number of pages	19
Journal	eLife
Volume	8
DOIs	https://doi.org/10.7554/eLife.48686
Publication status	Published - 23 Sept 2019

ASJC Scopus subject areas

General Neuroscience
General Immunology and Microbiology
General Biochemistry,Genetics and Molecular Biology

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10.7554/eLife.48686Licence: CC BY

Final Published VersionFinal published version, 1.59 MBLicence: CC BY

Cite this

@article{f1d8ee4820984edc97482ef773338d6b,

title = "TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication",

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.",

author = "Remi Sonneville and Rahul Bhowmick and Saskia Hoffmann and Niels Mailand and Hickson, {Ian D.} and Karim Labib",

note = "We thank the Medical Research Council for funding (core grant MC_UU_12016/13 to KL), together with Cancer Research U.K. (Programme Grant C578/A24558), the Wellcome Trust (reference 102943/Z/13/Z for an Investigator award to KL), the Danish National Research Foundation (DNRF115; to IDH), the Danish Medical Research Council (DFF-4004-00155B; a postdoctoral fellowship grant to RB), and the European Research Council (grant no. 616236 to NM).",

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doi = "10.7554/eLife.48686",

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AU - Sonneville, Remi

AU - Bhowmick, Rahul

AU - Hoffmann, Saskia

AU - Mailand, Niels

AU - Hickson, Ian D.

AU - Labib, Karim

N1 - We thank the Medical Research Council for funding (core grant MC_UU_12016/13 to KL), together with Cancer Research U.K. (Programme Grant C578/A24558), the Wellcome Trust (reference 102943/Z/13/Z for an Investigator award to KL), the Danish National Research Foundation (DNRF115; to IDH), the Danish Medical Research Council (DFF-4004-00155B; a postdoctoral fellowship grant to RB), and the European Research Council (grant no. 616236 to NM).

PY - 2019/9/23

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N2 - 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.

AB - 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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ER -

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

Abstract

ASJC Scopus subject areas

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Novel Genome Integrity Pathways that Regulate DNA Replication Termination in Metazoa

Functional Dissection of the Eukaryotic Replisome (Senior Investigator Award)

Labib, Karim

Cite this

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

Novel Genome Integrity Pathways that Regulate DNA Replication Termination in Metazoa

Functional Dissection of the Eukaryotic Replisome (Senior Investigator Award)

Profiles

Labib, Karim

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