ArticleMolecular cell2015
Distinct but Concerted Roles of ATR, DNA-PK, and Chk1 in Countering Replication Stress during S Phase.
Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 215 papers.
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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
215 citing papers in PubMed, 305 citations in OpenAlex.
- A Phase II Study of Berzosertib in Combination with Carboplatin Compared with Docetaxel with Carboplatin in Metastatic Castration-Resistant Prostate Cancer.Cancer research communications · 2026Trial
- An updated view on lagging strand DNA replication: implications for the replication stress response.Cell cycle (Georgetown, Tex.) · 2026Article
- Targeting common denominators of DNA damage tolerance mechanisms as therapeutic strategy to cope with dynamic phenotypic changes in triple-negative breast cancer cells.Cell death discovery · 2026Article
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- 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
- Heat shock protein family D member 1 (HSPD1) modulates ribosome-related pathways and protein synthesis in lung adenocarcinoma.Molecular and cellular biochemistry · 2026Article
- PTEN deficiency confers sensitivity to ATR inhibitor-based treatment in high-grade serous ovarian cancer.The Journal of clinical investigation · 2026Article
- CDT1 acts with the replisome to remodel replication forks.Science advances · 2026Article
- A functional landscape for chromosome 17q in neuroblastoma: balancing replication stress and genomic stability.British journal of cancer · 2026Review
- Inhibition of the ATR-CHK1 signaling pathway sensitizes MCPyV-positive Merkel cell carcinoma to gemcitabine.BMC cancer · 2026Article
- Distinct ATRX functions cooperate with 9-1-1 and CST complexes to safeguard replication and telomere integrity.Nature structural & molecular biology · 2026Article
- Prognostic, Predictive, and Clinical Relevance of DNA Damage Repair Alterations in Biliary Tract Cancers.Cancers · 2026Review
- Unsupervised Deep Representation Learning and Probabilistic Clustering for the Systems-Level Discovery of Germline Mutation Signatures in Pediatric Cancers.Biomedicines · 2026Article
- Common DNA Damage Response Factors Required for Cellular Resistance to Inhibitors for the Ataxia Telangiectasia and Rad3-Related Checkpoint Kinase in Hematopoietic Cells.Biomolecules · 2026Article
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- ATR enforcement of the S/G2 checkpoint prevents premature S phase shutdown and genome instability.bioRxiv : the preprint server for biology · 2026Article
- ATM counteracts chromatin-bound cGAS during DNA replication.Nature cell biology · 2026Article
- Microhomology-mediated end joining acts directly on replication forks to repair single-ended double-strand breaks.Molecular cell · 2026Article
- Precise control of transcription condensates across S phase balances linker histone expression with DNA replication, ensuring genome stability.Molecular cell · 2026Article
155 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The ATR-Chk1 pathway is critical for DNA damage responses and cell-cycle progression. Chk1 inhibition is more deleterious to cycling cells than ATR inhibition, raising questions about ATR and Chk1 functions in the absence of extrinsic replication stress. Here we show that a key role of ATR in S phase is to coordinate RRM2 accumulation and origin firing. ATR inhibitor (ATRi) induces massive ssDNA accumulation and replication catastrophe in a fraction of early S-phase cells. In other S-phase cells, however, ATRi induces moderate ssDNA and triggers a DNA-PK and Chk1-mediated backup pathway to suppress origin firing. The backup pathway creates a threshold such that ATRi selectively kills cells under high replication stress, whereas Chk1 inhibitor induces cell death at a lower threshold. The levels of ATRi-induced ssDNA correlate with ATRi sensitivity in a panel of cell lines, suggesting that ATRi-induced ssDNA could be predictive of ATRi sensitivity in cancer cells.
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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.