Low Replicative Stress Triggers Cell-Type Specific Inheritable Advanced Replication Timing

DNA replication timing (RT), reflecting the temporal order of origin activation, is known as a robust and conserved cell-type specific process. Upon low replication stress, the slowing of replication forks induces well-documented RT delays associated to genetic instability, but it can also generate...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-05, Vol.22 (9), p.4959
Main Authors: Courtot, Lilas, Bournique, Elodie, Maric, Chrystelle, Guitton-Sert, Laure, Madrid-Mencía, Miguel, Pancaldi, Vera, Cadoret, Jean-Charles, Hoffmann, Jean-Sébastien, Bergoglio, Valérie
Format: Article
Language:English
Subjects:
Aphidicolin
Cell cycle
Cell division
Cell lines
Chromatin
chromatin accessibility
Colorectal cancer
Deoxyribonucleic acid
DNA
DNA biosynthesis
DNA damage
DNA replication stress
DNA replication timing
Domains
Epigenetics
Experiments
Gene expression
Genetic engineering
Genomes
Genomic instability
Heterochromatin
Life Sciences
Replication
Replication forks
Replication origins
Temporal variations
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Summary:DNA replication timing (RT), reflecting the temporal order of origin activation, is known as a robust and conserved cell-type specific process. Upon low replication stress, the slowing of replication forks induces well-documented RT delays associated to genetic instability, but it can also generate RT advances that are still uncharacterized. In order to characterize these advanced initiation events, we monitored the whole genome RT from six independent human cell lines treated with low doses of aphidicolin. We report that RT advances are cell-type-specific and involve large heterochromatin domains. Importantly, we found that some major late to early RT advances can be inherited by the unstressed next-cellular generation, which is a unique process that correlates with enhanced chromatin accessibility, as well as modified replication origin landscape and gene expression in daughter cells. Collectively, this work highlights how low replication stress may impact cellular identity by RT advances events at a subset of chromosomal domains.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22094959