In this study, we developed novel double-membranous non-viral gene delivery system modified with SV-40 T antigen-derived nuclear localization signal (NLS-DMEND) for delivery of luciferase plasmid DNA to nucleus of non-dividing mouse bone marrow-derived dendritic cells (BMDC). Intracellular trafficking and gene expression of NLS-DMEND in the BMDC were evaluated. Condensed DNA was observed in the nucleus by confocal laser scanning microscopy, and the NLS-DMEND induced significant luciferase activity in the BMDC. It was suggested that the condensed DNA particle transferred into nucleus via energy dependent manner, since the nuclear transfer was inhibited by metabolic inhibitors. In conclusion, condensed plasmid DNA was delivered into the nucleus of non-dividing BMDC by NLS-DMEND.
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http://dx.doi.org/10.1248/bpb.29.1290 | DOI Listing |
RNA polymerase II (RNAPII) is regulated by sequence-specific transcription factors (TFs) and the pre-initiation complex (PIC): TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, Mediator. TFs and Mediator contain intrinsically-disordered regions (IDRs) and form phase-separated condensates, but how IDRs control RNAPII function remains poorly understood. Using purified PIC factors, we developed a Real-time In-vitro Fluorescence Transcription assay (RIFT) for second-by-second visualization of RNAPII transcription at hundreds of promoters simultaneously.
View Article and Find Full Text PDFJ Mol Biol
January 2025
Department of Biology, Carnegie Mellon University, Pittsburgh, PA 15213, USA. Electronic address:
Alternative Lengthening of Telomeres (ALT) pathway is a telomerase-independent mechanism that utilizes homology-directed repair (HDR) to sustain telomere length in specific cancers. Biomolecular condensates, such as ALT-associated promyelocytic leukemia nuclear bodies (APBs), have emerged as critical players in the ALT pathway, supporting telomere maintenance in ALT-positive cells. These condensates bring together DNA repair proteins, telomeric repeats, and other regulatory elements.
View Article and Find Full Text PDFUltrastruct Pathol
January 2025
Department of Histochemistry and Cell Biology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Breast cancer patients experience more severe emotional distress and depression compared to those with other cancers. Selective serotonin reuptake inhibitors (SSRIs), like citalopram, are commonly used to treat depression. However, the link between SSRI use and breast cancer progression is debated.
View Article and Find Full Text PDFMethods Cell Biol
January 2025
Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Seville, Spain; Cancer Division, Faculty of medicine, Imperial college London, United Kingdom.
Histones are essential nuclear proteins that package eukaryotic DNA into chromosomes, play a vital role in gene regulation, DNA replication, DNA repair and chromosome condensation. Understanding histone modifications is crucial for grasping biological and disease-related processes. Specific alterations in histone modifications serve as sensitive and selective biomarkers for conditions like cancer, impacting both tumor and immune cells and affecting their interactions.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of General Surgery, The First Affiliated Hospital of University of Science and Technology of China, Key Laboratory of Immune Response and Immunotherapy, Center for Advanced Interdisciplinary Science Interdisciplinary Science & Biomedicine of Institute of Health and Medicine, Division of Life Sciences & Medicine, University of Science and Technology of China, Hefei 230027, Anhui, China.
The DNA-sensing protein cGAS plays a pivotal role in the innate immune response and pathogenesis of various diseases. DNA triggers liquid-liquid phase separation (LLPS) and enhances the enzymatic activity of cGAS. However, the regulatory mechanisms of the disordered N terminus remain unclear.
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