Based on genome-scale loss-of-function screens we discovered that Topoisomerase III-β (TOP3B), a human topoisomerase that acts on DNA and RNA, is required for yellow fever virus and dengue virus-2 replication. Remarkably, we found that TOP3B is required for efficient replication of all positive-sense-single stranded RNA viruses tested, including SARS-CoV-2. While there are no drugs that specifically inhibit this topoisomerase, we posit that TOP3B is an attractive anti-viral target.
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http://dx.doi.org/10.1016/j.antiviral.2020.104874 | DOI Listing |
Sci Rep
January 2025
Department of Hematology and Oncology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children's Hospital of Chongqing Medical University, No 136 Zhongshan 2 road, YuZhong district, Chongqing, 400014, China.
Genetic alterations play a pivotal role in leukemic clonal transformation, significantly influencing disease pathogenesis and clinical outcomes. Here, we report a novel fusion gene and investigate its pathogenic role in acute lymphoblastic leukemia (ALL). We engineer a transposon transfection system expressing the TOP2B::AFF2 transcript and introduce it into Ba/F3 cells.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt.
Ciprofloxacin, a widely used second-generation fluoroquinolone for treating bacterial infections, has recently shown notable anticancer properties. This review explores progress in developing ciprofloxacin derivatives with anticancer properties, emphasizing key structural changes that improve their therapeutic effectiveness by modifying the basic group at position 7, the carboxylic acid group at position 3, or both. It further investigates the mechanisms by which these derivatives fight cancer, such as inducing apoptosis, arresting the cell cycle, inhibiting topoisomerase I and II, preventing tubulin polymerization, suppressing interleukin 6, blocking thymidine phosphorylase, inhibiting multidrug resistance proteins, and hindering angiogenesis.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea.
Topoisomerase II inhibitors, particularly etoposide, have long been integral to the treatment of lung cancer, especially small cell lung cancer. This review comprehensively examines the mechanisms of action of etoposide, its clinical efficacy, and its role in current lung cancer treatment regimens. Etoposide exerts its anticancer effects by inducing DNA strand breaks through the inhibition of topoisomerase II, leading to cancer cell apoptosis.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78712, USA.
Glioblastoma (GBM), the most prevalent primary malignant brain tumor, remains challenging to treat due to extensive inter- and intra-tumor heterogeneity. This variability demands combination treatments to improve therapeutic outcomes. A significant obstacle in treating GBM is the expression of O-methylguanine-DNA methyltransferase, a DNA repair enzyme that reduces the efficacy of the standard alkylating agent, temozolomide, in about 50% of patients.
View Article and Find Full Text PDFGenes (Basel)
January 2025
Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Via Ferrata 9, 27100 Pavia, Italy.
DNA damage response (DDR) is a highly conserved and complex signal transduction network required for preserving genome integrity. DNA repair pathways downstream of DDR include the tyrosyl-DNA phosphodiesterase1 (TDP1) enzyme that hydrolyses the phosphodiester bond between the tyrosine residue of topoisomerase I (TopI) and 3'-phosphate end of DNA. A small TDP1 subfamily, composed of TDP1α and TDP1β, is present in plants.
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