ArticleMolecular cell2021
cGAS phase separation inhibits TREX1-mediated DNA degradation and enhances cytosolic DNA sensing.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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Who cites it
125 citing papers in PubMed, 185 citations in OpenAlex.
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- The cGAS-STING pathway: mechanistic basis, dual biological functions and translational therapeutic advances.Apoptosis : an international journal on programmed cell death · 2026Review
- The cGAS-STING pathway in inflammaging and neuroinflammation.Science China. Life sciences · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Molecular mechanisms regulating cGAS/STING activation in health and disease.The Journal of clinical investigation · 2026Review
- Multiaxial Biophysical Control of Oncogenic Phase Separation by Indoleamines: A Proof-of-Concept Synthesis of Landscape-Level Regulation.Journal of pineal research · 2026Review
- Selective targeting of human TREX1 exonuclease by small molecule inhibitors is mediated by a conformational switch.NAR molecular medicine · 2026Article
- Spotlight on cGAS-STING: role in disease pathogenesis and therapeutic potential.Molecular biomedicine · 2026Review
- A designed peptide disrupting viral protease cleavage restores cGAS-DNA phase separation and type I interferon responses.PLoS pathogens · 2026Article
- Electrostatic bimodality of human cytosolic DNA sensor cGAS-dsDNA condensates revealed by millisecond flashing electrophoretic separation.Nature communications · 2026Article
- Protein•DNA mesh assembly drives dsDNA-specific and duplex length-dependent activation of cGAS.bioRxiv : the preprint server for biology · 2026Article
- Review
- Extracellular cGAMP in health and disease.Molecular biomedicine · 2026Review
- Enterovirus A71 3AB protein facilitates immune evasion by blocking cGAS recognition of mtDNA.EMBO reports · 2026Article
- Phase Separation of NFIB Suppresses SLC3A2-Mediated Ferroptosis in Castration-Resistant Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CSDE1 promotes viral immune evasion through RNA-dependent and phosphorylation-modulated liquid-liquid phase separation.Nature communications · 2026Article
- Targeting phase separation: a new strategy to disrupt the stromal-immune axis in colorectal cancer.Cell communication and signaling : CCS · 2026Review
- ELISA-Based Enzyme Kinetics Assay for Measuring cGAS Activity.Bio-protocol · 2026Article
- The cGAS-STING pathway in cancer: friend or foe.Cell death & disease · 2026Review
- Biochemical Engineering Perspective on cGAS: From Enzyme Discovery to Potential Industrial Application.Chembiochem : a European journal of chemical biology · 2026Review
65 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cyclic GMP-AMP synthase (cGAS) recognition of cytosolic DNA is critical for the immune response to cancer and pathogen infection. Here, we discover that cGAS-DNA phase separation is required to resist negative regulation and allow efficient sensing of immunostimulatory DNA. We map the molecular determinants of cGAS condensate formation and demonstrate that phase separation functions to limit activity of the cytosolic exonuclease TREX1. Mechanistically, phase separation forms a selective environment that suppresses TREX1 catalytic function and restricts DNA degradation to an outer shell at the droplet periphery. We identify a TREX1 mutation associated with the severe autoimmune disease Aicardi-Goutières syndrome that increases penetration of TREX1 into the repressive droplet interior and specifically impairs degradation of phase-separated DNA. Our results define a critical function of cGAS-DNA phase separation and reveal a molecular mechanism that balances cytosolic DNA degradation and innate immune activation.
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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.