Skip to Main content Skip to Navigation
Preprints, Working Papers, ...

Low replication stress leads to specific replication timing advances associated to chromatin remodelling in cancer cells

Résumé : DNA replication is well orchestrated in mammalian cells through a tight regulation of the temporal order of replication origin activation, named the replication timing, a robust and conserved process in each cell type. Upon low replication stress, the slowing of replication forks induces delayed replication of fragile regions leading to genetic instability. The impact of low replication stress on the replication timing in different cellular backgrounds has not been explored yet. Here we analysed the whole genome replication timing in a panel of 6 human cell lines under low replication stress. We first demonstrated that cancer cells were more impacted than non-tumour cells. Strikingly, we unveiled an enrichment of specific replication domains undergoing a switch from late to early replication in some cancer cells. We found that advances in replication timing correlate with heterochromatin regions poorly sensitive to DNA damage signalling while being subject to an increase of chromatin accessibility. Finally, our data indicate that, following release from replication stress conditions, replication timing advances can be inherited by the next cellular generation, suggesting a new mechanism by which cancer cells would adapt to cellular or environmental stress.
Abstract : DNA replication is well orchestrated in mammalian cells through a tight regulation of the temporal order of replication origin activation, named the replication timing, a robust and conserved process in each cell type. Upon low replication stress, the slowing of replication forks induces delayed replication of fragile regions leading to genetic instability. The impact of low replication stress on the replication timing in different cellular backgrounds has not been explored yet. Here we analysed the whole genome replication timing in a panel of 6 human cell lines under low replication stress. We first demonstrated that cancer cells were more impacted than non-tumour cells. Strikingly, we unveiled an enrichment of specific replication domains undergoing a switch from late to early replication in some cancer cells. We found that advances in replication timing correlate with heterochromatin regions poorly sensitive to DNA damage signalling while being subject to an increase of chromatin accessibility. Finally, our data indicate that, following release from replication stress conditions, replication timing advances can be inherited by the next cellular generation, suggesting a new mechanism by which cancer cells would adapt to cellular or environmental stress.
Document type :
Preprints, Working Papers, ...
Complete list of metadatas

Cited literature [99 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-03006823
Contributor : Chrystelle Maric Antoinat <>
Submitted on : Tuesday, November 17, 2020 - 3:36:17 PM
Last modification on : Monday, November 30, 2020 - 12:40:06 PM

File

2020.08.19.256883v3.full.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Lilas Courtot, Elodie Bournique, Chrystelle Maric, Laure Guitton-Sert, Miguel Madrid-Mencía, et al.. Low replication stress leads to specific replication timing advances associated to chromatin remodelling in cancer cells. 2020. ⟨hal-03006823⟩

Share

Metrics

Record views

10

Files downloads

18