ArticleThe EMBO journal2019
Chromatin-bound cGAS is an inhibitor of DNA repair and hence accelerates genome destabilization and cell death.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 2 of them syntheses that pooled it.
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Who cites it
171 citing papers in PubMed, 2 syntheses or guidelines pooled it, 248 citations in OpenAlex.
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- cGAS in nucleus: The link between immune response and DNA damage repair.Frontiers in immunology · 2022Pooled it
- Loss of killifish cGAS attenuates age-related signatures but does not affect organismal life span.EMBO reports · 2026Article
- Targeting cancer-intrinsic protein neddylation bypasses the loss of JAK/STAT signaling and overcomes acquired resistance to immunotherapy.Research square · 2026Article
- Innate immune crosstalk in ALS/FTD pathogenesis.Cell insight · 2026Review
- A dual role for cGAS in shaping cellular and organismal responses to genomic instability.Genes & development · 2026Article
- cGAS restricts PARP1-mediated microhomology-mediated end joining by suppressing poly-ADP-ribosylation.Cell death and differentiation · 2026Article
- Protein•DNA mesh assembly drives dsDNA-specific and duplex length-dependent activation of cGAS.bioRxiv : the preprint server for biology · 2026Article
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Human cGAS Drives LINE-1 Transcriptional Activation to Trigger MAVS-Dependent Cellular Senescence.Aging cell · 2026Article
- Micronuclei: origins, assays, mechanisms, diseases and treatments.Signal transduction and targeted therapy · 2026Review
- C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer.iScience · 2026Review
- Telomere Crisis Shapes Cancer Evolution.Cold Spring Harbor perspectives in biology · 2026Review
- Opportunities and challenges of targeting cGAS-STING in cancer.Nature reviews. Cancer · 2026Review
- Energy-sensing molecule RORγ regulates cholesterol metabolism and immune signaling in diabetic kidney disease and aging.Nature communications · 2026Article
- STING agonist diABZI confers protection against swine acute diarrhea syndrome coronavirus in neonatal mice by activating antiviral immunity.Journal of virology · 2026Article
- The longevity code in four letters (amino acids).Chinese medical journal · 2026Article
- The radiotherapy induced cyclic GMP-AMP-synthase re-localization and immune signature predicts HNSCC treatment efficacy.Communications medicine · 2026Article
- PARP1 trapping activates cGAS-STING pathway to induce immunogenic cell death in multiple myeloma.Cancer cell international · 2026Article
- A Novel FGFR3-Targeting Antibody-Drug Conjugate Induces Tumor Cell Apoptosis through the cGAS-STING Pathway in Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
111 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
DNA repair via homologous recombination (HR) is indispensable for genome integrity and cell survival but if unrestrained can result in undesired chromosomal rearrangements. The regulatory mechanisms of HR are not fully understood. Cyclic GMP-AMP synthase (cGAS) is best known as a cytosolic innate immune sensor critical for the outcome of infections, inflammatory diseases, and cancer. Here, we report that cGAS is primarily a chromatin-bound protein that inhibits DNA repair by HR, thereby accelerating genome destabilization, micronucleus generation, and cell death under conditions of genomic stress. This function is independent of the canonical STING-dependent innate immune activation and is physiologically relevant for irradiation-induced depletion of bone marrow cells in mice. Mechanistically, we demonstrate that inhibition of HR repair by cGAS is linked to its ability to self-oligomerize, causing compaction of bound template dsDNA into a higher-ordered state less amenable to strand invasion by RAD51-coated ssDNA filaments. This previously unknown role of cGAS has implications for understanding its involvement in genome instability-associated disorders including 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.