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Replication Stress in Mammalian Cells and Its Consequences for Mitosis

The faithful transmission of genetic information to daughter cells is central to maintaining genomic stability and relies on the accurate and complete duplication of genetic material during each cell cycle. However, the genome is routinely exposed to endogenous and exogenous stresses that can impede...

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Autores principales: Gelot, Camille, Magdalou, Indiana, Lopez, Bernard S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488665/
https://www.ncbi.nlm.nih.gov/pubmed/26010955
http://dx.doi.org/10.3390/genes6020267
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author Gelot, Camille
Magdalou, Indiana
Lopez, Bernard S.
author_facet Gelot, Camille
Magdalou, Indiana
Lopez, Bernard S.
author_sort Gelot, Camille
collection PubMed
description The faithful transmission of genetic information to daughter cells is central to maintaining genomic stability and relies on the accurate and complete duplication of genetic material during each cell cycle. However, the genome is routinely exposed to endogenous and exogenous stresses that can impede the progression of replication. Such replication stress can be an early cause of cancer or initiate senescence. Replication stress, which primarily occurs during S phase, results in consequences during mitosis, jeopardizing chromosome segregation and, in turn, genomic stability. The traces of replication stress can be detected in the daughter cells during G1 phase. Alterations in mitosis occur in two types: 1) local alterations that correspond to breaks, rearrangements, intertwined DNA molecules or non-separated sister chromatids that are confined to the region of the replication dysfunction; 2) genome-wide chromosome segregation resulting from centrosome amplification (although centrosomes do not contain DNA), which amplifies the local replication stress to the entire genome. Here, we discuss the endogenous causes of replication perturbations, the mechanisms of replication fork restart and the consequences for mitosis, chromosome segregation and genomic stability.
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spelling pubmed-44886652015-07-02 Replication Stress in Mammalian Cells and Its Consequences for Mitosis Gelot, Camille Magdalou, Indiana Lopez, Bernard S. Genes (Basel) Review The faithful transmission of genetic information to daughter cells is central to maintaining genomic stability and relies on the accurate and complete duplication of genetic material during each cell cycle. However, the genome is routinely exposed to endogenous and exogenous stresses that can impede the progression of replication. Such replication stress can be an early cause of cancer or initiate senescence. Replication stress, which primarily occurs during S phase, results in consequences during mitosis, jeopardizing chromosome segregation and, in turn, genomic stability. The traces of replication stress can be detected in the daughter cells during G1 phase. Alterations in mitosis occur in two types: 1) local alterations that correspond to breaks, rearrangements, intertwined DNA molecules or non-separated sister chromatids that are confined to the region of the replication dysfunction; 2) genome-wide chromosome segregation resulting from centrosome amplification (although centrosomes do not contain DNA), which amplifies the local replication stress to the entire genome. Here, we discuss the endogenous causes of replication perturbations, the mechanisms of replication fork restart and the consequences for mitosis, chromosome segregation and genomic stability. MDPI 2015-05-22 /pmc/articles/PMC4488665/ /pubmed/26010955 http://dx.doi.org/10.3390/genes6020267 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Gelot, Camille
Magdalou, Indiana
Lopez, Bernard S.
Replication Stress in Mammalian Cells and Its Consequences for Mitosis
title Replication Stress in Mammalian Cells and Its Consequences for Mitosis
title_full Replication Stress in Mammalian Cells and Its Consequences for Mitosis
title_fullStr Replication Stress in Mammalian Cells and Its Consequences for Mitosis
title_full_unstemmed Replication Stress in Mammalian Cells and Its Consequences for Mitosis
title_short Replication Stress in Mammalian Cells and Its Consequences for Mitosis
title_sort replication stress in mammalian cells and its consequences for mitosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488665/
https://www.ncbi.nlm.nih.gov/pubmed/26010955
http://dx.doi.org/10.3390/genes6020267
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