ArticleScience immunology2020
Human DNA-PK activates a STING-independent DNA sensing pathway.
Article in Science immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.
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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
122 citing papers in PubMed, 1 synthesis or guideline pooled it, 174 citations in OpenAlex.
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- One virus-many strategies: type-specific interactions between human adenoviruses and innate immunity.Journal of virology · 2026Review
- Dataset of RNA-seq profiles from THP-1-derived macrophages pretreated with AZD7648 and stimulated with CT DNA.Data in brief · 2026Article
- Article
- Histone H3.3 ensures cell proliferation and genomic stability during myeloid cell development.iScience · 2026Article
- The proteomics and phosphoproteomics landscape of melanoma under T cell attack.Cell reports. Medicine · 2026Article
- DNA-PKcs inhibition sensitizes glioblastoma to radiotherapy through reprogramming of tumor cell states and immune microenvironment cell types.Research square · 2026Article
- DNA-PK interacts with cyclic dinucleotides and inhibits type I interferon responses.The Journal of experimental medicine · 2026Article
- Interferon stimulatory DNA activates the DNA damage signaling through ATM and DNA-PK sensing.The Journal of biological chemistry · 2026Article
- Mitochondrial DNA as a driver of inflammation via the cGAS-STING pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- DNA-PK-mediated phosphorylation of STAT6 establishes a non-canonical type 2 immunity axis to prevent macrophage senescence.Nature communications · 2026Article
- Targeting NHEJ activates STING signaling through MYC degradation to boost antitumor immunity in SCLC.Nature communications · 2026Article
- Oncolytic viruses: advanced strategies in cancer therapy.Signal transduction and targeted therapy · 2026Review
- DNA-PKcs orchestrates CTLA-4 depletion-induced senescence in cancer cells.Cell death & disease · 2026Article
- DNA-PKcs controls the cytotoxic T cell response to cancer and transplant allograft through regulating LAT-dependent signaling.Cell reports · 2026Article
- Sterile inflammation in laminopathies.European journal of cell biology · 2025Review
- The methyl-CpG-binding protein 2 inhibits cGAS-associated signaling.Nature communications · 2025Article
- PRRs-Dependent and Independent Mechanisms of STING Signaling in Inflammatory and Autoimmune Diseases.Biomedicines · 2025Review
- RPA1 protects DNA damage-induced PANoptosis in limb development.Science advances · 2025Article
- Review
62 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Detection of intracellular DNA by the cGAS-STING pathway activates a type I interferon-mediated innate immune response that protects from virus infection. Whether there are additional DNA sensing pathways, and how such pathways might function, remains controversial. We show here that humans-but not laboratory mice-have a second, potent, STING-independent DNA sensing pathway (SIDSP). We identify human DNA-dependent protein kinase (DNA-PK) as the sensor of this pathway and demonstrate that DNA-PK activity drives a robust and broad antiviral response. We show that the E1A oncoprotein of human adenovirus 5 and the ICP0 protein of herpes simplex virus 1 block this response. We found heat shock protein HSPA8/HSC70 as a target for inducible phosphorylation in the DNA-PK antiviral pathway. Last, we demonstrate that DNA damage and detection of foreign DNA trigger distinct modalities of DNA-PK activity. These findings reveal the existence, sensor, a specific downstream target, and viral antagonists of a SIDSP in human 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.