ArticleInternational journal of molecular sciences2025
In and out of Replication Stress: PCNA/RPA1-Based Dynamics of Fork Stalling and Restart in the Same Cell.
Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- Ubiquitin and SUMO pathways in DNA replication and replication-coupled repair.Critical reviews in biochemistry and molecular biologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Replication forks encounter various impediments, which induce fork stalling and threaten genome stability, yet the precise dynamics of fork stalling and restart at the single-cell level remain elusive. Herein, we devise a live-cell microscopy-based approach to follow hydroxyurea-induced fork stalling and subsequent restart at 30 s resolution. We measure two distinct processes during fork stalling. One is rapid PCNA removal, which reflects the drop in DNA synthesis. The other is gradual RPA1 accumulation up to 2400 nt of ssDNA per fork despite an active intra-S checkpoint. Restoring the nucleotide pool enables a prompt restart without post-replicative ssDNA and a smooth cell cycle progression. ATR, but not ATM inhibition, accelerates hydroxyurea-induced RPA1 accumulation nine-fold, leading to RPA1 exhaustion within 20 min. Fork restart under ATR inhibition led to the persistence of ~600 nt ssDNA per fork after S-phase, which reached 2500 nt under ATR/ATM co-inhibition, with both scenarios leading to mitotic catastrophe. MRE11 inhibition had no effect on PCNA/RPA1 dynamics regardless of ATR activity. E3 ligase RAD18 was recruited at stalled replication forks in parallel to PCNA removal. Our results shed light on fork dynamics during nucleotide depletion and provide a valuable tool for interrogating the effects of replication stress-inducing anti-cancer agents.
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Registered trials
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