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Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship

The replication-timing program constitutes a key element of the organization and coordination of numerous nuclear processes in eukaryotes. This program is established at a crucial moment in the cell cycle and occurs simultaneously with the organization of the genome, thus indicating the vital signif...

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Autores principales: Briu, Lina-Marie, Maric, Chrystelle, Cadoret, Jean-Charles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125245/
https://www.ncbi.nlm.nih.gov/pubmed/33946274
http://dx.doi.org/10.3390/ijms22094764
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author Briu, Lina-Marie
Maric, Chrystelle
Cadoret, Jean-Charles
author_facet Briu, Lina-Marie
Maric, Chrystelle
Cadoret, Jean-Charles
author_sort Briu, Lina-Marie
collection PubMed
description The replication-timing program constitutes a key element of the organization and coordination of numerous nuclear processes in eukaryotes. This program is established at a crucial moment in the cell cycle and occurs simultaneously with the organization of the genome, thus indicating the vital significance of this process. With recent technological achievements of high-throughput approaches, a very strong link has been confirmed between replication timing, transcriptional activity, the epigenetic and mutational landscape, and the 3D organization of the genome. There is also a clear relationship between replication stress, replication timing, and genomic instability, but the extent to which they are mutually linked to each other is unclear. Recent evidence has shown that replication timing is affected in cancer cells, although the cause and consequence of this effect remain unknown. However, in-depth studies remain to be performed to characterize the molecular mechanisms of replication-timing regulation and clearly identify different cis- and trans-acting factors. The results of these studies will potentially facilitate the discovery of new therapeutic pathways, particularly for personalized medicine, or new biomarkers. This review focuses on the complex relationship between replication timing, replication stress, and genomic instability.
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spelling pubmed-81252452021-05-17 Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship Briu, Lina-Marie Maric, Chrystelle Cadoret, Jean-Charles Int J Mol Sci Review The replication-timing program constitutes a key element of the organization and coordination of numerous nuclear processes in eukaryotes. This program is established at a crucial moment in the cell cycle and occurs simultaneously with the organization of the genome, thus indicating the vital significance of this process. With recent technological achievements of high-throughput approaches, a very strong link has been confirmed between replication timing, transcriptional activity, the epigenetic and mutational landscape, and the 3D organization of the genome. There is also a clear relationship between replication stress, replication timing, and genomic instability, but the extent to which they are mutually linked to each other is unclear. Recent evidence has shown that replication timing is affected in cancer cells, although the cause and consequence of this effect remain unknown. However, in-depth studies remain to be performed to characterize the molecular mechanisms of replication-timing regulation and clearly identify different cis- and trans-acting factors. The results of these studies will potentially facilitate the discovery of new therapeutic pathways, particularly for personalized medicine, or new biomarkers. This review focuses on the complex relationship between replication timing, replication stress, and genomic instability. MDPI 2021-04-30 /pmc/articles/PMC8125245/ /pubmed/33946274 http://dx.doi.org/10.3390/ijms22094764 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Briu, Lina-Marie
Maric, Chrystelle
Cadoret, Jean-Charles
Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship
title Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship
title_full Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship
title_fullStr Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship
title_full_unstemmed Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship
title_short Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship
title_sort replication stress, genomic instability, and replication timing: a complex relationship
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125245/
https://www.ncbi.nlm.nih.gov/pubmed/33946274
http://dx.doi.org/10.3390/ijms22094764
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