ArticleDNA repair2012
Defects in DNA degradation revealed in crystal structures of TREX1 exonuclease mutations linked to autoimmune disease.
Article in DNA repair, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Scalable production of monovalent streptavidin with high yield and purity.Scientific reports · 2026Article
- Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Towards precision medicine for systemic lupus erythematosus and neuropsychiatric manifestations.Expert review of precision medicine and drug development · 2025Article
- Three Prime Repair Exonuclease 1 preferentially degrades the integration-incompetent HIV-1 DNA through favorable kinetics, thermodynamic, structural and conformational properties.bioRxiv : the preprint server for biology · 2024Article
- Neuropsychiatric Systemic Lupus Erythematosus: Molecules Involved in Its Imunopathogenesis, Clinical Features, and Treatment.Molecules (Basel, Switzerland) · 2024Review
- Molecular insight into the specific enzymatic properties of TREX1 revealing the diverse functions in processing RNA and DNA/RNA hybrids.Nucleic acids research · 2023Article
- Multiple RNA- and DNA-binding proteins exhibit direct transfer of polynucleotides with implications for target-site search.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- TREX1 cytosolic DNA degradation correlates with autoimmune disease and cancer immunity.Clinical and experimental immunology · 2023Article
- Structural basis of human TREX1 DNA degradation and autoimmune disease.Nature communications · 2022Article
- TREX1 as a Novel Immunotherapeutic Target.Frontiers in immunology · 2021Article
- TREX1 - Apex predator of cytosolic DNA metabolism.DNA repair · 2020Article
- The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders.International review of cell and molecular biology · 2019Review
- Structural basis for overhang excision and terminal unwinding of DNA duplexes by TREX1.PLoS biology · 2018Article
- Aicardi-Goutières syndrome protein TREX1 suppresses L1 and maintains genome integrity through exonuclease-independent ORF1p depletion.Nucleic acids research · 2017Article
- Human DNA Exonuclease TREX1 Is Also an Exoribonuclease That Acts on Single-stranded RNA.The Journal of biological chemistry · 2015Article
- Exonuclease TREX1 degrades double-stranded DNA to prevent spontaneous lupus-like inflammatory disease.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Human disease phenotypes associated with mutations in TREX1.Journal of clinical immunology · 2015Review
- Recent Insights into the Control of Human Papillomavirus (HPV) Genome Stability, Loss, and Degradation.Journal of clinical medicine · 2015Article
- The Arg-62 residues of the TREX1 exonuclease act across the dimer interface contributing to catalysis in the opposing protomers.The Journal of biological chemistry · 2014Article
- Update on pathogenesis and treatment of CLE.Current opinion in rheumatology · 2013Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Mutations within the human TREX1 3' exonuclease are associated with Aicardi-Goutières Syndrome (AGS) and familial chilblain lupus (FCL). Both AGS and FCL are autoimmune diseases that result in increased levels of interferon alpha and circulating antibodies to DNA. TREX1 is a member of the endoplasmic reticulum (ER)-associated SET complex and participates in granzyme A-mediated cell death to degrade nicked genomic DNA. The loss of TREX1 activity may result in the accumulation of double-stranded DNA (dsDNA) degradation intermediates that trigger autoimmune activation. The X-ray crystal structures of the TREX1 wt apoprotein, the dominant D200H, D200N and D18N homodimer mutants derived from AGS and FCL patients, as well as the recessive V201D homodimer mutant have been determined. The structures of the D200H and D200N mutant proteins reveal the enzyme has lost coordination of one of the active site metals, and the catalytic histidine (H195) is trapped in a conformation pointing away from the active site. The TREX1 D18N and V201D mutants are able to bind both metals in the active site, but with inter-metal distances that are larger than optimal for catalysis. Additionally, all of the mutant structures reveal a reduced mobility in the catalytic histidine, providing further explanation for the loss of catalytic activity. The structures of the mutant TREX1 proteins provide insight into the dysfunction relating to human disease. Additionally, the TREX1 apoprotein structure together with the previously determined wild type substrate and product structures allow us to propose a distinct mechanism for the TREX1 exonuclease.
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