ArticleMolecular cell2025
The DNA replication checkpoint prevents PCNA/RFC depletion to protect forks from HLTF-induced collapse in human cells.
Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- An updated view on lagging strand DNA replication: implications for the replication stress response.Cell cycle (Georgetown, Tex.) · 2026Article
- SPHINX31 acts as a SRPK1 inhibitor targeting the ATR/DNA-PKcs/CHK1 replicative checkpoint to inhibit cell growth in non-small cell lung cancer.Molecular oncology · 2026Article
- Plant-specific and conserved mechanisms of the polymerase-associated factor 1 complex in replication stress responses.Nature plants · 2026Article
- Hijacking of host PCNA by circovirus replication-associated protein to recruit POLD1 drives viral DNA replication and is inhibited by R428.PLoS pathogens · 2026Article
- Direct visualization of MCM helicase activation and replisome coupling in situ.bioRxiv : the preprint server for biology · 2026Article
- Replication origin flexibility: a tool to mitigate the hazards of excess replication.Trends in genetics : TIG · 2026Review
- Topological stress regulates replication fork dynamics in unperturbed S phase.Nature communications · 2026Article
- Increased replication-associated single-stranded DNA promotes formaldehyde-induced mutagenesis.bioRxiv : the preprint server for biology · 2026Article
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- The expanding roles of homologous recombination proteins in genome stability.The EMBO journal · 2026Review
- Regulated TRESLIN-MTBP loading governs initiation zones and replication timing in human DNA replication.Nature communications · 2025Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- Stn1 supports Mec1 function in protecting stalled replication forks from degradation.PLoS genetics · 2025Article
- Leading and lagging strand abasic sites differentially affect vertebrate replisome progression but involve analogous bypass mechanisms.Nucleic acids research · 2025Article
- The DNA replication checkpoint limits Okazaki fragment accumulation to protect and restart stalled forks.Molecular cell · 2025Article
- Ubiquitin and SUMO pathways in DNA replication and replication-coupled repair.Critical reviews in biochemistry and molecular biologyReview
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Authors and funding
8 authors.
Funding
Abstract
The DNA replication checkpoint is crucial for maintaining genome stability after genotoxic stress; without it, stalled DNA replication forks cannot restart normally, excess DNA replication origins are activated, DNA damage and single-stranded DNA (ssDNA) accumulate, S phase does not finish, and cells die. Preventing excess origin firing suppresses all these effects. Here, we show in human cells that when replication is not restrained by a functional checkpoint, excess DNA synthesis sequesters the processivity factor PCNA and its loader, replication factor C (RFC), preventing normal fork restart. Nascent DNA ends unprotected by RFC/PCNA are attacked by the helicase-like transcription factor (HLTF), causing irreversible replication fork collapse and hyperaccumulation of ssDNA. This explains how the checkpoint stabilizes stalled replication forks and has implications for how origin firing is normally coordinated with fork progression. Loss of HLTF suppresses fork collapse and cell lethality in checkpoint-deficient cells, which has implications for how resistance to anti-checkpoint therapies may arise.
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