Low Replicative Stress Triggers Cell-Type Specific Inheritable Advanced Replication Timing
Open Access
- 7 May 2021
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (9), 4959
- https://doi.org/10.3390/ijms22094959
Abstract
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.Funding Information
- Ligue Nationale Contre le Cancer (RS16/75-108, ANR-18-IDEX-0001, RS17/75-135, PLBIO2016-10493)
This publication has 90 references indexed in Scilit:
- Genome-scale analysis of replication timing: from bench to bioinformaticsNature Protocols, 2011
- 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stressNature, 2011
- Cell-type-specific replication initiation programs set fragility of the FRA3B fragile siteNature, 2011
- G2 phase chromatin lacks determinants of replication timingThe Journal of cell biology, 2010
- Domain-wide regulation of DNA replication timing during mammalian developmentChromosome Research, 2009
- The FANC pathway and BLM collaborate during mitosis to prevent micro-nucleation and chromosome abnormalitiesNature, 2009
- Replication fork movement sets chromatin loop size and origin choice in mammalian cellsNature, 2008
- Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replicationProceedings of the National Academy of Sciences of the United States of America, 2008
- Domain organization of human chromosomes revealed by mapping of nuclear lamina interactionsNature, 2008
- Activation of the DNA damage checkpoint and genomic instability in human precancerous lesionsNature, 2005