ArticlePLoS biology2018
Structural basis for overhang excision and terminal unwinding of DNA duplexes by TREX1.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Immune response to DNA and RNA: structural insights, molecular mechanisms, and therapeutic targeting.Molecular biomedicine · 2026Review
- Disordered DNA-binding motif forms a modulation site for inhibiting the cancer immunotherapy target TREX1.Nucleic acids research · 2026Article
- Prevalence and impact of molecular variation in the three-prime repair exonuclease 1 TREX1 and its implications for oncology.Human genomics · 2025Article
- Effect of methyl DNA adducts on 3'-5' exonuclease activity of human TREX1.The Biochemical journal · 2025Article
- Structural and biochemical characterization of the mitomycin C repair exonuclease MrfB.Nucleic acids research · 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
- Structural and biochemical characterization of the mitomycin C repair exonuclease MrfB.bioRxiv : the preprint server for biology · 2024Article
- Molecular insight into the specific enzymatic properties of TREX1 revealing the diverse functions in processing RNA and DNA/RNA hybrids.Nucleic acids research · 2023Article
- PML and PML-like exonucleases restrict retrotransposons in jawed vertebrates.Nucleic acids research · 2023Article
- TREX1 cytosolic DNA degradation correlates with autoimmune disease and cancer immunity.Clinical and experimental immunology · 2023Article
- Molecular Mechanisms of Neutrophil Extracellular Trap (NETs) Degradation.International journal of molecular sciences · 2023Review
- Structural basis of human TREX1 DNA degradation and autoimmune disease.Nature communications · 2022Article
- Chemical and Biomolecular Strategies for STING Pathway Activation in Cancer Immunotherapy.Chemical reviews · 2022Review
- Article
- DNA End Joining: G0-ing to the Core.Biomolecules · 2021Review
- Perspectives on formaldehyde dysregulation: Mitochondrial DNA damage and repair in mammalian cells.DNA repair · 2021Review
- cGAS phase separation inhibits TREX1-mediated DNA degradation and enhances cytosolic DNA sensing.Molecular cell · 2021Article
- Understanding APE1 cellular functions by the structural preference of exonuclease activities.Computational and structural biotechnology journal · 2021Review
- The Role of Nucleases and Nucleic Acid Editing Enzymes in the Regulation of Self-Nucleic Acid Sensing.Frontiers in immunology · 2021Review
- Structural insights into the duplex DNA processing of TREX2.Nucleic acids research · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Three prime repair exonuclease 1 (TREX1) is an essential exonuclease in mammalian cells, and numerous in vivo and in vitro data evidenced its participation in immunity regulation and in genotoxicity remediation. In these very complicated cellular functions, the molecular mechanisms by which duplex DNA substrates are processed are mostly elusive because of the lack of structure information. Here, we report multiple crystal structures of TREX1 complexed with various substrates to provide the structure basis for overhang excision and terminal unwinding of DNA duplexes. The substrates were designed to mimic the intermediate structural DNAs involved in various repair pathways. The results showed that the Leu24-Pro25-Ser26 cluster of TREX1 served to cap the nonscissile 5'-end of the DNA for precise removal of the short 3'-overhang in L- and Y-structural DNA or to wedge into the double-stranded region for further digestion along the duplex. Biochemical assays were also conducted to demonstrate that TREX1 can indeed degrade double-stranded DNA (dsDNA) to a full extent. Overall, this study provided unprecedented knowledge at the molecular level on the enzymatic substrate processing involved in prevention of immune activation and in responses to genotoxic stresses. For example, Arg128, whose mutation in TREX1 was linked to a disease state, were shown to exhibit consistent interaction patterns with the nonscissile strand in all of the structures we solved. Such structure basis is expected to play an indispensable role in elucidating the functional activities of TREX1 at the cellular level and in vivo.
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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.