Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 14 of 14 for “"TREX1"”.
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TREX1 DNASE ACTIVITY IS REGULATED BY PHOSPHORYLATION AND MACROPHAGES LACKING TREX1 HAVE IMPAIRED EFFEREOCYTOSIS
TREX1 is a 3′ to 5′ exonuclease found in metazoan cells. TREX1 acts on both ssDNA and dsDNA and functions to prevent adverse immune activation by degrading cytosolic nucleic acids that would otherwise activate DNA sensors resulting in interferon production. Mutations in TREX1 cause multifactoral, …
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TREX1 AUTOIMMUNE DISEASE MUTANTS REVEAL DIMERIC STRUCTURE REQUIREMENTS AND THE C-TERMINAL REGION OF TREX1 CONTROLS CELL LOCALIZATION THROUGH UBIQUITINATION
Mutations in the TREX1 3'' exonuclease cause a spectrum of autoimmune disorders in humans. In this study, we elucidate how structural features of TREX1 that are necessary for normal TREX1 biological function are perturbed and lead to disease. TREX1 is a homodimeric enzyme, and the Arg-114 residue …
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Studies on the Mislocalized Exonuclease TREX1 that Causes a Systemic Vasculopathy
… retinopathy and impaired other organs caused by TREX1 mutations (CHARIOT) is a rare, autosomal dominant disease of middle-age onset with 100% penetrance that manifests primarily with visual disturbances and neurological symptoms due to small vessel occlusions in the retina and white matter of the …
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The role of TREX1 and TREX2 in cellular responses to cisplatin
… cells identified the 3’ to 5’ exonucleases TREX1 and TREX2 as significantly upregulated DDR genes. Increased expression was confirmed at the protein level in two distinct cancer cell lines. Individual depletion of TREX1 and TREX2 had no effect on cell viability under basal conditions but …
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Structural and Biochemical Examination of Aberrant dsDNA Metabolism in TREX1-associated Autoimmunity
TREX1 is a 3’ exonuclease that degrades both single– and double–stranded polynucleotides in order to facilitate orderly cell death and prevent immune dysfunction. Mutations in the TREX1 gene at positions Asp–18 and Asp–200 lead to dominant autoimmune phenotypes …
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The TREX1 3' Exonuclease and Autoimmune Disease: Structural and Biochemical Analysis of Disease Mutants Involved in Autoimmune Dysfunction
The homodimeric TREX1 protein is a member of the DnaQ family of exonucleases and catalyzes the major 3′ exonuclease activity detected in mammalian cell extracts. Mutations within the Trex1 gene are the underlying cause of multiple autoimmune diseases including Aicardi-Goutières syndrome (AGS), …
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Regulation of type I interferons in murine dendritic cells
… 2 (STAT2) and Three prime Repair EXonuclease 1 (Trex1), in DC biology. Our research furthers our understanding of DC development, activation and function, and provides important data for the therapeutic application of modified DCs to induce immunological tolerance in gene therapy, IFN-dependent …
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TREX1 C-Terminus Regulates Oligosaccharyltransfererase to Prevent the Accumulation of an Endogenous Bioactive Disaccharide Associated with Autoimmune Disorders
… leading toautoimmunity. DNase III, also known as TREX1, is one of negative regulators of CDS-mediated innate immune response. TREX1 is a 314 amino acid endoplasmic reticulum (ER) tail-anchored 3' exonuclease where the N-terminal region contains the DNase domain and the C-terminal end controls …
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Regulation of the cGAS-STING Pathway: Non-Agonist Activation and Cellular Trafficking
… cGAS-STING pathway is to inhibit cytosolic DNase TREX1, which would lead to the build-up of self-DNA in the cytosol and activation of cGAS. TREX1 expression is upregulated during radiation therapy and TREX1 knockdown promotes anti-tumor immunity. I developed a cell-free DNase assay that …
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Roles of Cyclic GMP-AMP Synthase in Immune Defense Against Retroviruses and Autoimmunity
… however, overactive cGAS causes autoimmunity. TREX1 is a cytosolic DNase which clears mislocalized DNA in the cytosol. Loss-of-function mutations in TREX1 cause the human disease Aicardi-Goutières syndrome (AGS). AGS manifests with abnormal type I IFN production and inflammation in multiple …
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Genetics of Cerebral Small Vessel Disease
… SVD, such as COL4A1/A2, HTRA1, FOXC1 and TREX1. Genome wide association studies (GWAS) have also revealed loci associated with sporadic SVD strokes and its related features. This thesis explores the genetic basis of SVD primarily from the angle of the ‘one gene, one disease’ hypothesis. We …
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Ribonuclease H2, RNA:DNA hybrids and innate immunity
… cellular functions of two other AGS proteins, TREX1 and SAMHD1. Therefore, no clear evidence was found for the direct involvement of RNase H2 in the innate immune response to nucleic acids. An alternative model for the pathogenesis of disease hypothesises that decreased RNase H2 activity within …
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Understanding Genomes Through Engineered Structural Variation
… and made the discovery that 3’ flap nucleases TREX1 and TREX2 suppressed the insertion of longer sequences. I further delineated the effects of nucleotide composition and secondary structure of the insertion sequence on editing rates. Next, I targeted a prime editor to the high copy number …