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Cell Mol Life Sci
March 2025
Institute for Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Medizinisch-Theoretisches Zentrum MTZ, Technische Universität Dresden, Fiedlerstraße 42, 01307, Dresden, Germany.
Signal peptide peptidase (SPP) is an ER-resident aspartyl intramembrane protease cleaving proteins within type II-oriented transmembrane segments. Here, we identified the tail-anchored protein Three prime repair exonuclease 1 (TREX1) as a novel substrate of SPP. Based on its DNase activity, TREX1 removes cytosolic DNA acting as a negative regulator of the DNA-sensing cGAS/STING pathway.
View Article and Find Full Text PDFFront Immunol
March 2025
IMMUNO-GRAM (Infection and IMMunity Genetic Research to Advance Molecular Medicine) Center of Reference, Research Institute - McGill University Health Centre, Montreal, QC, Canada.
Background: Aicardi-Goutières syndrome (AGS) is a rare monogenic type I interferonopathy characterized by dysregulated inflammation and tissue damage that primarily affects the central nervous system. AGS is genetically diverse, with pathogenic variants across multiple genes, including TREX1, which drives excessive type I interferon (IFN) production.
Objective: This study investigated the genetic and molecular mechanisms underlying AGS in a family of two affected children, focusing on the role of variants in protein expression and dysregulation of the interferon pathway.
Commun Biol
March 2025
Institut Pasteur, Université Paris Cité, CNRS UMR 3528, Unit of Architecture and Dynamics of Biological Macromolecules, 75724, Paris, France.
BsmI, a thermophilic Type IIS restriction endonuclease from Bacillus stearothermophilus, presents a unique structural composition, housing two distinct active sites within a single monomer. Recognition of the non-symmetrical 5'-GAATGC-3' sequence enables precise cleavage of the top and bottom DNA strands. Synthetic biology interventions have led to the transformation of BsmI into Nb.
View Article and Find Full Text PDFNucleic Acids Res
February 2025
Structural Biology Laboratory, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.
Single-stranded DNA (ssDNA) is an important intermediate generated during various cellular DNA transactions, primarily during long-patch base excision repair. When displaced by DNA polymerase during strand displacement DNA synthesis, ssDNA forms 5' overhangs (flaps) that are either cleaved by DNA nucleases or protected from degradation upon binding of single-stranded DNA-binding proteins (SSB). Several nucleases are involved in the removal of ssDNA flaps in human mitochondria, namely the endonucleases FEN1 and DNA2, as well as the exonuclease MGME1.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
February 2025
Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky; Markey Cancer Center, University of Kentucky, Lexington, Kentucky. Electronic address:
Prostate cancer, particularly castration-resistant prostate cancer, remains a serious public health issue. Androgen signaling inhibitors have emerged as a major treatment approach but with limited success. Thus, identification of novel treatment targets is of high clinical relevance.
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