ArticleNature communications2016
RPA and Rad51 constitute a cell intrinsic mechanism to protect the cytosol from self DNA.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 2 of them syntheses that pooled it.
What it found
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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
108 citing papers in PubMed, 2 syntheses or guidelines pooled it, 160 citations in OpenAlex.
- cGAS in nucleus: The link between immune response and DNA damage repair.Frontiers in immunology · 2022Pooled it
- Systemic Lupus Erythematosus and DNA Degradation and Elimination Defects.Frontiers in immunology · 2019Pooled it
- Autoinflammatory syndromes of STING and TREX1 dysfunction.The Journal of clinical investigation · 2026Review
- Interferon stimulatory DNA activates the DNA damage signaling through ATM and DNA-PK sensing.The Journal of biological chemistry · 2026Article
- The expanding roles of homologous recombination proteins in genome stability.The EMBO journal · 2026Review
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- PRRs-Dependent and Independent Mechanisms of STING Signaling in Inflammatory and Autoimmune Diseases.Biomedicines · 2025Review
- Activation and regulation of cGAS-STING signaling in cancer cells.Molecular cell · 2025Review
- Targeting Innate Immune Checkpoint TREX1 Is a Safe and Effective Immunotherapeutic Strategy in Cancer.Cancer research · 2025Article
- Role of DEAD/DEAH-box helicases in immunity, infection and cancers.Cell communication and signaling : CCS · 2025Review
- The DNase TREX1 is a substrate of the intramembrane protease SPP with implications for disease pathogenesis.Cellular and molecular life sciences : CMLS · 2025Article
- Epidermal ZBP1 stabilizes mitochondrial Z-DNA to drive UV-induced IFN signaling in autoimmune photosensitivity.Science immunology · 2025Article
- Effect of methyl DNA adducts on 3'-5' exonuclease activity of human TREX1.The Biochemical journal · 2025Article
- Article
- Prime Editor Gene Therapy and TREX1 Mosaicism in Retinal Vasculopathy with Cerebral Leukoencephalopathy.Journal of clinical immunology · 2024Article
- The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench.Immunological reviews · 2024Review
- Immune evasion: An imperative and consequence of MYC deregulation.Molecular oncology · 2024Review
- Monogenic lupus - from gene to targeted therapy.Molecular and cellular pediatrics · 2024Review
- Mutations in the non-catalytic polyproline motif destabilize TREX1 and amplify cGAS-STING signaling.Human molecular genetics · 2024Article
- Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans.Nature communications · 2024Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded DNA (ssDNA) continuously arises during the repair of DNA damage induced by endogenous and environmental genotoxic stress. Here we show that short ssDNA traverses the nuclear membrane, but is drawn into the nucleus by binding to the DNA replication and repair factors RPA and Rad51. Knockdown of RPA and Rad51 enhances cytosolic leakage of ssDNA resulting in cGAS-dependent type I IFN activation. Mutations in the exonuclease TREX1 cause type I IFN-dependent autoinflammation and autoimmunity. We demonstrate that TREX1 is anchored within the outer nuclear membrane to ensure immediate degradation of ssDNA leaking into the cytosol. In TREX1-deficient fibroblasts, accumulating ssDNA causes exhaustion of RPA and Rad51 resulting in replication stress and activation of p53 and type I IFN. Thus, the ssDNA-binding capacity of RPA and Rad51 constitutes a cell intrinsic mechanism to protect the cytosol from self DNA.
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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.