ArticleeLife2016
Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 51 citations in OpenAlex.
- Prognostic impact of ATM mutations in patients with metastatic colorectal cancer.Scientific reports · 2019Trial
- 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
- ATM-kinase deficiency triggers early multi-compartment remodeling of the cerebellar microenvironment.Acta neuropathologica communications · 2026Article
- The BRCA1-A complex restricts replication fork reversal-dependent DNA repair in ATM deficient cells.bioRxiv : the preprint server for biology · 2026Article
- Article
- Long-Term Survival Following Chemoradiation in Locoregional Recurrent GermlineAdvances in radiation oncology · 2025Article
- Inactive Parp2 causes Tp53-dependent lethal anemia by blocking replication-associated nick ligation in erythroblasts.Molecular cell · 2024Article
- ATM and 53BP1 regulate alternative end joining-mediated V(D)J recombination.Science advances · 2024Article
- Ataxia-Telangiectasia Mutated Loss-of-Function Displays Variant and Tissue-Specific Differences across Tumor Types.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- cGAS-STING signalling regulates microglial chemotaxis in genome instability.Nucleic acids research · 2024Article
- Deregulated kinase action in prostate cancer: molecular basis and therapeutic implications.Endocrine-related cancer · 2023Review
- Inactive PARP1 causes embryonic lethality and genome instability in a dominant-negative manner.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- ATM depletion induces proteasomal degradation of FANCD2 and sensitizes neuroblastoma cells to PARP inhibitors.BMC cancer · 2023Article
- Cellular functions of the protein kinase ATM and their relevance to human disease.Nature reviews. Molecular cell biology · 2021Review
- Review
- Poly-ADP-ribosylation drives loss of protein homeostasis in ATM and Mre11 deficiency.Molecular cell · 2021Article
- Article
- Cancer genome datamining and functional genetic analysis implicate mechanisms of ATM/ATR dysfunction underpinning carcinogenesis.Communications biology · 2021Article
- The Cancer-Associated ATM R3008H Mutation Reveals the Link between ATM Activation and Its Exchange.Cancer research · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Missense mutations in ATM kinase, a master regulator of DNA damage responses, are found in many cancers, but their impact on ATM function and implications for cancer therapy are largely unknown. Here we report that 72% of cancer-associated ATM mutations are missense mutations that are enriched around the kinase domain. Expression of kinase-dead ATM (Atm(KD/-)) is more oncogenic than loss of ATM (Atm(-/-)) in mouse models, leading to earlier and more frequent lymphomas with Pten deletions. Kinase-dead ATM protein (Atm-KD), but not loss of ATM (Atm-null), prevents replication-dependent removal of Topo-isomerase I-DNA adducts at the step of strand cleavage, leading to severe genomic instability and hypersensitivity to Topo-isomerase I inhibitors. Correspondingly, Topo-isomerase I inhibitors effectively and preferentially eliminate Atm(KD/-), but not Atm-proficientor Atm(-/-) leukemia in animal models. These findings identify ATM kinase-domain missense mutations as a potent oncogenic event and a biomarker for Topo-isomerase I inhibitor based therapy.
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What OpenQuestion holds
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.