ArticleEMBO reports2024
Embryonic stem cells maintain high origin activity and slow forks to coordinate replication with cell cycle progression.
Article in EMBO reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Adaptive Replication Fork Acceleration by CDK1-Cyclin B1 Sustains Genome Duplication despite Impaired Origin Firing.bioRxiv : the preprint server for biology · 2026Article
- Morphogen Gradients as Drivers of Mosaicism During Early Human Development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Wnt10b signaling regulates replication stress-induced chromosomal instability in human cancer.Life science alliance · 2025Article
- Decoding nucleoside supplementation: how thymidine outperforms ribonucleosides in accelerating mammalian replication forks.Nucleic acids research · 2025Article
- Stem Cell for Cancer Immunotherapy: Current Approaches and Challenges.Stem cell reviews and reports · 2025Review
- Polymerase-usage sequencing identifies initiation zones with less bias across S phase in mouse embryonic stem cells.Journal of biochemistry · 2025Article
- Impact of G1 phase kinetics on the acquisition of stemness in cancer cells: the critical role of cyclin D.Molecular biology reports · 2025Review
Corrections and comments
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Authors and funding
3 authors.
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Abstract
Embryonic stem (ES) cells are pluripotent stem cells that can produce all cell types of an organism. ES cells proliferate rapidly and are thought to experience high levels of intrinsic replication stress. Here, by investigating replication fork dynamics in substages of S phase, we show that mammalian pluripotent stem cells maintain a slow fork speed and high active origin density throughout the S phase, with little sign of fork pausing. In contrast, the fork speed of non-pluripotent cells is slow at the beginning of S phase, accompanied by increased fork pausing, but thereafter fork pausing rates decline and fork speed rates accelerate in an ATR-dependent manner. Thus, replication fork dynamics within the S phase are distinct between ES and non-ES cells. Nucleoside addition can accelerate fork speed and reduce origin density. However, this causes miscoordination between the completion of DNA replication and cell cycle progression, leading to genome instability. Our study indicates that fork slowing in the pluripotent stem cells is an integral aspect of DNA replication.
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Registered trials
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