ArticleCell research2020
Structural basis for nucleosome-mediated inhibition of cGAS activity.
Article in Cell research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- cGAS in nucleus: The link between immune response and DNA damage repair.Frontiers in immunology · 2022Pooled it
- TREX1 limits anti-tumor immunity by degrading short cytosolic DNA molecules.EMBO reports · 2026Article
- Dynamic phosphorylation of cGAS by DNA-PKcs and PPP1CC balances DNA repair and innate immunity.Medical oncology (Northwood, London, England) · 2026Article
- cGAS-STING pathway modulation: A new hope for neural regeneration.Neural regeneration research · 2026Article
- A versatile cGAMP reporter reveals principles of cGAS activation by DNA damage and chromosome instability.Nature cell biology · 2026Article
- Cytoplasmic relocation of nuclear Ku70 by Bruceine A augments cGAS-STING pathway-mediated anti-tumor immunity.Acta pharmaceutica Sinica. B · 2026Article
- Molecular mechanisms regulating cGAS/STING activation in health and disease.The Journal of clinical investigation · 2026Review
- ATM counteracts chromatin-bound cGAS during DNA replication.Nature cell biology · 2026Article
- The cGAS-STING pathway at the crossroads of neuroimmunology: bridging innate immunity to aging and neurodegeneration.Biomarker research · 2026Review
- Distinct Domains Contribute to the Subcellular Localization of Human cGAS in Yeast.Biomolecules · 2026Article
- PCBP1 binding to single-stranded poly-cytosine motifs enhances cGAS sensing and impairs breast cancer development.Communications biology · 2026Article
- cGAS-STING pathway in innate immunity and its cell-specific role in kidney diseases.Frontiers in immunology · 2026Review
- Breaking barriers: The cGAS-STING pathway as a novel frontier in cancer immunotherapy.Cancer communications (London, England) · 2025Review
- Pseudorabies virus DNA polymerase processivity factor pUL42 inhibits type I IFN production by negatively regulating cGAS-STING signaling pathway.Journal of virology · 2025Article
- Activation and regulation of cGAS-STING signaling in cancer cells.Molecular cell · 2025Review
- Review
- The cGAS-STING axis: a comprehensive review from immune defense to disease pathogenesis.Immunologic research · 2025Review
- Emerging role of the cGAS-STING pathway in cardiovascular diseases: biologic function, mechanisms and targeted therapy.Molecular medicine (Cambridge, Mass.) · 2025Review
- Regulation of cGAS-STING signalling and its diversity of cellular outcomes.Nature reviews. Immunology · 2025Review
- cGAS-STING: mechanisms and therapeutic opportunities.Science China. Life sciences · 2025Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of cyclic GMP-AMP synthase (cGAS) through sensing cytosolic double stranded DNA (dsDNA) plays a pivotal role in innate immunity against exogenous infection as well as cellular regulation under stress. Aberrant activation of cGAS induced by self-DNA is related to autoimmune diseases. cGAS accumulates at chromosomes during mitosis or spontaneously in the nucleus. Binding of cGAS to the nucleosome competitively attenuates the dsDNA-mediated cGAS activation, but the molecular mechanism of the attenuation is still poorly understood. Here, we report two cryo-electron microscopy structures of cGAS-nucleosome complexes. The structures reveal that cGAS interacts with the nucleosome as a monomer, forming 1:1 and 2:2 complexes, respectively. cGAS contacts the nucleosomal acidic patch formed by the H2A-H2B heterodimer through the dsDNA-binding site B in both complexes, and could interact with the DNA from the other symmetrically placed nucleosome via the dsDNA-binding site C in the 2:2 complex. The bound nucleosome inhibits the activation of cGAS through blocking the interaction of cGAS with ligand dsDNA and disrupting cGAS dimerization. R236A or R255A mutation of cGAS impairs the binding between cGAS and the nucleosome, and largely relieves the nucleosome-mediated inhibition of cGAS activity. Our study provides structural insights into the inhibition of cGAS activity by the nucleosome, and advances the understanding of the mechanism by which hosts avoid the autoimmune attack caused by cGAS.
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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.