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

International journal of molecular sciences (2021-06-03)
Lilas Courtot, Elodie Bournique, Chrystelle Maric, Laure Guitton-Sert, Miguel Madrid-Mencía, Vera Pancaldi, Jean-Charles Cadoret, Jean-Sébastien Hoffmann, Valérie Bergoglio

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.

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Monoclonal Anti-α-Tubulin antibody produced in mouse, ascites fluid, clone B-5-1-2
SeqPlex DNA Amplification Kit, For use with high throughput sequencing technologies, Whole Genome Amplification kit designed to facilitate Next Gen Sequencing.