ArticleScience advances2021
MRE11-dependent instability in mitochondrial DNA fork protection activates a cGAS immune signaling pathway.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
36 citing papers in PubMed, 45 citations in OpenAlex.
- Mitochondrial mechanisms underlying spatial immune phenotypes in non‑small cell lung cancer: Implications for ICI response and cold‑to‑hot tumor conversion (Review).Oncology reports · 2026Review
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- The immunology behind inflammaging-causes, sources, and mechanisms.The Journal of allergy and clinical immunology · 2026Review
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- Parkinson's disease linked LRRK2 G2019S drives oxidative nuclear DNA damage and PARP1 hyperactive signaling.bioRxiv : the preprint server for biology · 2026Article
- Ultrarare Variants in DNA Damage Repair and Mitochondrial Genes in Pediatric Acute-Onset Neuropsychiatric Syndrome and Acute Behavioral Regression in Neurodevelopmental Disorders.Developmental neuroscience · 2026Article
- The Fanconi anemia pathway repairs colibactin-induced DNA interstrand cross-links.Nature communications · 2025Article
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- Mitochondrial DNA signals driving immune responses: Why, How, Where?Cell communication and signaling : CCS · 2025Review
- Mitochondrial DNA in Exercise-Mediated Innate Immune Responses.International journal of molecular sciences · 2025Review
- To cleave or not and how? The DNA exonucleases and endonucleases in immunity.Genes & diseases · 2025Review
- Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders.Journal of neuroinflammation · 2025Review
- MRE11-independent effects of Mirin on mitochondrial DNA integrity and cellular immune responses.Molecular biology of the cell · 2025Article
- Exploring the pathogenesis of MAFLD from an immunological perspective: from the perspective of the cGAS/STING/NF-κB signaling pathway.Frontiers in immunology · 2025Review
- Ultrarare Variants in DNA Damage Repair Genes in Pediatric Acute-Onset Neuropsychiatric Syndrome or Acute Behavioral Regression in Neurodevelopmental Disorders.Developmental neuroscience · 2025Article
- Subset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation.Science immunology · 2024Article
- When DNA-damage responses meet innate and adaptive immunity.Cellular and molecular life sciences : CMLS · 2024Review
- Dual deficiency of melatonin and dihydrotestosterone promotes stromal cell damage and mediates prostatitis via the cGAS-STING pathway in sleep-deprived mice.Cell communication and signaling : CCS · 2024Article
- The cGAS-STING pathway: a therapeutic target in diabetes and its complications.Burns & trauma · 2024Review
- DNA sensing of dendritic cells in cancer immunotherapy.Frontiers in molecular biosciences · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Mitochondrial DNA (mtDNA) instability activates cGAS-dependent innate immune signaling by unknown mechanisms. Here, we find that Fanconi anemia suppressor genes are acting in the mitochondria to protect mtDNA replication forks from instability. Specifically, Fanconi anemia patient cells show a loss of nascent mtDNA through MRE11 nuclease degradation. In contrast to DNA replication fork stability, which requires pathway activation by FANCD2-FANCI monoubiquitination and upstream FANC core complex genes, mitochondrial replication fork protection does not, revealing a mechanistic and genetic separation between mitochondrial and nuclear genome stability pathways. The degraded mtDNA causes hyperactivation of cGAS-dependent immune signaling resembling the unphosphorylated ISG3 response. Chemical inhibition of MRE11 suppresses this innate immune signaling, identifying MRE11 as a nuclease responsible for activating the mtDNA-dependent cGAS/STING response. Collective results establish a previously unknown molecular pathway for mtDNA replication stability and reveal a molecular handle to control mtDNA-dependent cGAS activation by inhibiting MRE11 nuclease.
Identifiers
What OpenQuestion holds
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.