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DNA replication stress triggers rapid DNA replication fork breakage by Artemis and XPF

DNA replication stress (DRS) leads to the accumulation of stalled DNA replication forks leaving a fraction of genomic loci incompletely replicated, a source of chromosomal rearrangements during their partition in mitosis. MUS81 is known to limit the occurrence of chromosomal instability by processin...

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Autores principales: Bétous, Rémy, Goullet de Rugy, Théo, Pelegrini, Alessandra Luiza, Queille, Sophie, de Villartay, Jean-Pierre, Hoffmann, Jean-Sébastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085069/
https://www.ncbi.nlm.nih.gov/pubmed/30059501
http://dx.doi.org/10.1371/journal.pgen.1007541
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author Bétous, Rémy
Goullet de Rugy, Théo
Pelegrini, Alessandra Luiza
Queille, Sophie
de Villartay, Jean-Pierre
Hoffmann, Jean-Sébastien
author_facet Bétous, Rémy
Goullet de Rugy, Théo
Pelegrini, Alessandra Luiza
Queille, Sophie
de Villartay, Jean-Pierre
Hoffmann, Jean-Sébastien
author_sort Bétous, Rémy
collection PubMed
description DNA replication stress (DRS) leads to the accumulation of stalled DNA replication forks leaving a fraction of genomic loci incompletely replicated, a source of chromosomal rearrangements during their partition in mitosis. MUS81 is known to limit the occurrence of chromosomal instability by processing these unresolved loci during mitosis. Here, we unveil that the endonucleases ARTEMIS and XPF-ERCC1 can also induce stalled DNA replication forks cleavage through non-epistatic pathways all along S and G2 phases of the cell cycle. We also showed that both nucleases are recruited to chromatin to promote replication fork restart. Finally, we found that rapid chromosomal breakage controlled by ARTEMIS and XPF is important to prevent mitotic segregation defects. Collectively, these results reveal that Rapid Replication Fork Breakage (RRFB) mediated by ARTEMIS and XPF in response to DRS contributes to DNA replication efficiency and limit chromosomal instability.
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spelling pubmed-60850692018-08-18 DNA replication stress triggers rapid DNA replication fork breakage by Artemis and XPF Bétous, Rémy Goullet de Rugy, Théo Pelegrini, Alessandra Luiza Queille, Sophie de Villartay, Jean-Pierre Hoffmann, Jean-Sébastien PLoS Genet Research Article DNA replication stress (DRS) leads to the accumulation of stalled DNA replication forks leaving a fraction of genomic loci incompletely replicated, a source of chromosomal rearrangements during their partition in mitosis. MUS81 is known to limit the occurrence of chromosomal instability by processing these unresolved loci during mitosis. Here, we unveil that the endonucleases ARTEMIS and XPF-ERCC1 can also induce stalled DNA replication forks cleavage through non-epistatic pathways all along S and G2 phases of the cell cycle. We also showed that both nucleases are recruited to chromatin to promote replication fork restart. Finally, we found that rapid chromosomal breakage controlled by ARTEMIS and XPF is important to prevent mitotic segregation defects. Collectively, these results reveal that Rapid Replication Fork Breakage (RRFB) mediated by ARTEMIS and XPF in response to DRS contributes to DNA replication efficiency and limit chromosomal instability. Public Library of Science 2018-07-30 /pmc/articles/PMC6085069/ /pubmed/30059501 http://dx.doi.org/10.1371/journal.pgen.1007541 Text en © 2018 Bétous et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Bétous, Rémy
Goullet de Rugy, Théo
Pelegrini, Alessandra Luiza
Queille, Sophie
de Villartay, Jean-Pierre
Hoffmann, Jean-Sébastien
DNA replication stress triggers rapid DNA replication fork breakage by Artemis and XPF
title DNA replication stress triggers rapid DNA replication fork breakage by Artemis and XPF
title_full DNA replication stress triggers rapid DNA replication fork breakage by Artemis and XPF
title_fullStr DNA replication stress triggers rapid DNA replication fork breakage by Artemis and XPF
title_full_unstemmed DNA replication stress triggers rapid DNA replication fork breakage by Artemis and XPF
title_short DNA replication stress triggers rapid DNA replication fork breakage by Artemis and XPF
title_sort dna replication stress triggers rapid dna replication fork breakage by artemis and xpf
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085069/
https://www.ncbi.nlm.nih.gov/pubmed/30059501
http://dx.doi.org/10.1371/journal.pgen.1007541
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