ArticleThe EMBO journal2020
ATR inhibition potentiates ionizing radiation-induced interferon response via cytosolic nucleic acid-sensing pathways.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 136 citations in OpenAlex.
- Targeting WRN Helicase in Microsatellite-Instable Colorectal Cancer Induces Antitumor Immunity through Extrachromosomal Circular DNA Release.Cancer research · 2026Article
- CXCL9-driven immune rewiring and tumor-intrinsic ATR signaling inhibition restore radiotherapy response in lung cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- ATR inhibition induces NF-κB-dependent immunogenicity in Merkel cell carcinoma independent of cGAS-STING.NPJ precision oncology · 2026Article
- Dynamic phosphorylation of cGAS by DNA-PKcs and PPP1CC balances DNA repair and innate immunity.Medical oncology (Northwood, London, England) · 2026Article
- Ceralasertib Plus Durvalumab in Chinese Patients with Advanced Solid Tumors: A Nonrandomized Clinical Trial.Oncology and therapy · 2026Article
- ATR activity regulates DNA replication and RNA polymerase II transcription during S-phase.iScience · 2026Article
- The cGAS/STING pathway in cancer: translating innate DNA sensing into therapeutic potential.The Journal of clinical investigation · 2026Review
- Tumor cell intrinsic dsRNA innate immune response triggered by PARP inhibitor is compromised in BRCA1-deficient breast cancer by repressing IRF3.Protein & cell · 2026Article
- Identification of highly immunogenic endogenous dsRNAs from cellular MDA5 filaments.bioRxiv : the preprint server for biology · 2026Article
- Aspartate deficiency amplifies cGAS-STING signaling in antitumor immunity.The Journal of clinical investigation · 2026Article
- Comprehensive analysis of DNA repair, morphological remodeling and immune-gene expression in patient-derived biliary tract carcinoma organoids following ionizing radiation.Medical molecular morphology · 2026Article
- ATR kinase inhibitors induce mitochondrial fission in CD8bioRxiv : the preprint server for biology · 2026Article
- ATM counteracts chromatin-bound cGAS during DNA replication.Nature cell biology · 2026Article
- ISGylation of γH2AX retains MDC1 and facilitates homologous recombination repair causing radioresistance in esophageal adenocarcinoma.The Journal of biological chemistry · 2026Article
- Old dogs-new tricks: multifaceted functions of MAVS beyond antivirus activity in human health and diseases.Cell & bioscience · 2025Review
- Article
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- PARP-1 in tumor complicated with depression-possible role and therapeutic perspective: a narrative review.Translational cancer research · 2025Review
- Delineating the short- and long-term impact of ionizing radiation on antigen-inexperienced CD8+ T cell subsets.JCI insight · 2025Article
- Tumor irradiation induced immunogenic response: the impact of DNA damage induction and misrepair.Radiation oncology (London, England) · 2025Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Mechanistic understanding of how ionizing radiation induces type I interferon signaling and how to amplify this signaling module should help to maximize the efficacy of radiotherapy. In the current study, we report that inhibitors of the DNA damage response kinase ATR can significantly potentiate ionizing radiation-induced innate immune responses. Using a series of mammalian knockout cell lines, we demonstrate that, surprisingly, both the cGAS/STING-dependent DNA-sensing pathway and the MAVS-dependent RNA-sensing pathway are responsible for type I interferon signaling induced by ionizing radiation in the presence or absence of ATR inhibitors. The relative contributions of these two pathways in type I interferon signaling depend on cell type and/or genetic background. We propose that DNA damage-elicited double-strand DNA breaks releases DNA fragments, which may either activate the cGAS/STING-dependent pathway or-especially in the case of AT-rich DNA sequences-be transcribed and initiate MAVS-dependent RNA sensing and signaling. Together, our results suggest the involvement of two distinct pathways in type I interferon signaling upon DNA damage. Moreover, radiation plus ATR inhibition may be a promising new combination therapy against cancer.
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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.