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Genes 2015, 6(2), 267-298; doi:10.3390/genes6020267

Replication Stress in Mammalian Cells and Its Consequences for Mitosis

Institut de Cancérologie Gustave Roussy, CNRS UMR 8200 and Université Paris Sud, Equipe labélisée “LIGUE 2014”, 114, Rue Edouard Vaillant, 94805 Villejuif, France
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Academic Editor: Peter Frank
Received: 14 April 2015 / Revised: 15 May 2015 / Accepted: 18 May 2015 / Published: 22 May 2015
(This article belongs to the Special Issue DNA Replication)
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Abstract

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. View Full-Text
Keywords: replication stress; mitosis; anaphase bridges; single-ended DSB; homologous recombination; centrosome; micronuclei; fragile sites replication stress; mitosis; anaphase bridges; single-ended DSB; homologous recombination; centrosome; micronuclei; fragile sites
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Gelot, C.; Magdalou, I.; Lopez, B.S. Replication Stress in Mammalian Cells and Its Consequences for Mitosis. Genes 2015, 6, 267-298.

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