ArticleGenes & development2013
ATR phosphorylates SMARCAL1 to prevent replication fork collapse.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 264 papers.
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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.
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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
264 citing papers in PubMed, 403 citations in OpenAlex.
- Trial
- An updated view on lagging strand DNA replication: implications for the replication stress response.Cell cycle (Georgetown, Tex.) · 2026Article
- Beyond conventional therapies: the evolution of targeted agents and immunotherapies in triple-negative breast cancer.Acta pharmacologica Sinica · 2026Review
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- Mechanistic insights into phosphorylation-driven activation and therapeutic inhibition of human ATR-ATRIP.Nature structural & molecular biology · 2026Article
- CDT1 acts with the replisome to remodel replication forks.Science advances · 2026Article
- RTF2 and CLASPIN localize CHK1 to the replication fork to control S-phase progression.Science advances · 2026Article
- The BRCA1-A complex restricts replication fork reversal-dependent DNA repair in ATM deficient cells.Nature communications · 2026Article
- Article
- A Landscape Analysis of Human SUMOylation.Molecular & cellular proteomics : MCP · 2026Article
- ATM counteracts chromatin-bound cGAS during DNA replication.Nature cell biology · 2026Article
- Distinct mechanisms of replication stress induced by oncogenic RAS and cyclin E1 converge on R-loop-dependent fork reversal.Nature communications · 2026Article
- Defective DNA Damage Response Is a Targetable Therapeutic Vulnerability in ESR1-Mutant Breast Cancer.Cancer research · 2026Article
- SMARCAL1 is a targetable synthetic lethal therapeutic vulnerability in ATRX-deficient gliomas that use alternative lengthening of telomeres.Neuro-oncology · 2026Article
- The BRCA1-A complex restricts replication fork reversal-dependent DNA repair in ATM deficient cells.bioRxiv : the preprint server for biology · 2026Article
- Deciphering molecular pathways in urological cancers: A gateway to precision therapeutics.Journal of advanced research · 2026Review
- Fork Reversal Safeguards Epigenetic Inheritance During Replication Stress.Research square · 2026Article
- Auranofin attenuates TOPBP1-mediated ATR replication stress response and improves chemotherapeutic response in breast tumor models.The Journal of clinical investigation · 2025Article
- RNF4 and USP7 coordinate spatial regulation of SLX4 stability within the PML nuclear bodies.Nucleic acids research · 2025Article
- Pathogenic variants in MAEA disrupt DNA replication fork stability and are associated with developmental abnormalities in humans.Science advances · 2025Article
204 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The DNA damage response kinase ataxia telangiectasia and Rad3-related (ATR) coordinates much of the cellular response to replication stress. The exact mechanisms by which ATR regulates DNA synthesis in conditions of replication stress are largely unknown, but this activity is critical for the viability and proliferation of cancer cells, making ATR a potential therapeutic target. Here we use selective ATR inhibitors to demonstrate that acute inhibition of ATR kinase activity yields rapid cell lethality, disrupts the timing of replication initiation, slows replication elongation, and induces fork collapse. We define the mechanism of this fork collapse, which includes SLX4-dependent cleavage yielding double-strand breaks and CtIP-dependent resection generating excess single-stranded template and nascent DNA strands. Our data suggest that the DNA substrates of these nucleases are generated at least in part by the SMARCAL1 DNA translocase. Properly regulated SMARCAL1 promotes stalled fork repair and restart; however, unregulated SMARCAL1 contributes to fork collapse when ATR is inactivated in both mammalian and Xenopus systems. ATR phosphorylates SMARCAL1 on S652, thereby limiting its fork regression activities and preventing aberrant fork processing. Thus, phosphorylation of SMARCAL1 is one mechanism by which ATR prevents fork collapse, promotes the completion of DNA replication, and maintains genome integrity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.