ArticleNature communications2019
ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
What it found
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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
129 citing papers in PubMed, 180 citations in OpenAlex.
- Molecular biomarkers as key determinants of outcome in mantle cell lymphoma: results from the FIL V-RBAC trial.Blood advances · 2026Trial
- A Phase II Trial of Niraparib in Patients with Advanced Pancreatic Cancer Harboring Pathogenic Variants in ATM, BRCA1, BRCA2, PALB2, and CHEK2.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Cambridge Neoadjuvant Cancer of the Prostate (CANCAP03): A Window Study into the Effects of Olaparib ± Degarelix in Primary Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Recent Advances in Therapy for the Neurodegenerative Disorder Ataxia-Telangiectasia.International journal of molecular sciences · 2026Review
- The BRCA1-A complex restricts replication fork reversal-dependent DNA repair in ATM deficient cells.Nature communications · 2026Article
- Ataxia telangiectasia mutated (ATM) kinase as a predictive biomarker in clinical oncology: implications for a precision treatment approach.Neoplasia (New York, N.Y.) · 2026Review
- Distinct repair outcomes from single and convergent replication fork collapse.Nature structural & molecular biology · 2026Article
- PARP1 trapping activates ATM-mediated NF-κB signaling independent of replication in response to TOP1 blockade.Nucleic acids research · 2026Article
- The BRCA1-A complex restricts replication fork reversal-dependent DNA repair in ATM deficient cells.bioRxiv : the preprint server for biology · 2026Article
- BRCA1-A and LIG4 complexes mediate ecDNA biogenesis and cancer drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Poly ADP Ribose Polymerase Inhibitors Potentiate Proton Therapy End-of-Range Effects by Accelerating Replication Forks and Promoting Transcription Conflict.International journal of radiation oncology, biology, physics · 2026Article
- Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- Article
- Downregulation of ZFP36L1 contributes to methotrexate resistance in osteosarcoma through enhanced NHEJ DNA repair mechanisms.Cell death & disease · 2025Article
- AtMCM10 facilitates SDSA-mediated intermolecular homologous recombination repair via liquid-liquid phase separation in DNA damage response.Nature communications · 2025Article
- Targeting DNA Damage Repair Pathways Beyond PARP Inhibition.Targeted oncology · 2025Review
- Transcriptional regulation of Ligase IV by an intronic regulatory element directs thymocyte development.Genes and immunity · 2025Article
- Pathogenic variants in MAEA disrupt DNA replication fork stability and are associated with developmental abnormalities in humans.Science advances · 2025Article
- A homozygous TRIP13 pathogenic variant associated with familiar oocyte arrest and prematurely condensed sperm chromosomes.Molecular cytogenetics · 2025Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 5 institutions in 3 countries.
Funding
Abstract
Mutations in the ATM tumor suppressor gene confer hypersensitivity to DNA-damaging chemotherapeutic agents. To explore genetic resistance mechanisms, we performed genome-wide CRISPR-Cas9 screens in cells treated with the DNA topoisomerase I inhibitor topotecan. Thus, we here establish that inactivating terminal components of the non-homologous end-joining (NHEJ) machinery or of the BRCA1-A complex specifically confer topotecan resistance to ATM-deficient cells. We show that hypersensitivity of ATM-mutant cells to topotecan or the poly-(ADP-ribose) polymerase (PARP) inhibitor olaparib reflects delayed engagement of homologous recombination at DNA-replication-fork associated single-ended double-strand breaks (DSBs), allowing some to be subject to toxic NHEJ. Preventing DSB ligation by NHEJ, or enhancing homologous recombination by BRCA1-A complex disruption, suppresses this toxicity, highlighting a crucial role for ATM in preventing toxic LIG4-mediated chromosome fusions. Notably, suppressor mutations in ATM-mutant backgrounds are different to those in BRCA1-mutant scenarios, suggesting new opportunities for patient stratification and additional therapeutic vulnerabilities for clinical exploitation.
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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.