DNA supercoiling plays essential role in maintaining proper chromosome structure, as well as the equilibrium between genome dynamics and stability under specific physicochemical and physiological conditions. In mesophilic organisms, DNA is negatively supercoiled and, until recently, positive supercoiling was considered a peculiar mark of (hyper)thermophilic archaea needed to survive high temperatures. However, several lines of evidence suggest that negative and positive supercoiling might coexist in both (hyper)thermophilic and mesophilic organisms, raising the possibility that positive supercoiling might serve as a regulator of various cellular events, such as chromosome condensation, gene expression, mitosis, sister chromatid cohesion, centromere identity and telomere homoeostasis.
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bioRxiv
January 2025
Mechanisms of Epigenetic Inheritance, Department of Developmental and Stem Cell Biology, Institut Pasteur, UMR 3738, CNRS, Paris 75015, France.
Transcription introduces torsional stress in the DNA fiber causing it to transition from a relaxed to a supercoiled state that can propagate across several kilobases and modulate the binding and activity of DNA-associated proteins. As a result, transcription at one locus has the potential to impact nearby transcription events. In this study, we asked how DNA supercoiling affects histone modifications and transcription of neighboring genes in the multicellular eukaryote .
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Medicines Discovery Institute, Cardiff University, Cardiff CF10 3AT, UK.
DNA gyrase is a bacterial type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology and an archetypical target of antibiotics. The widely used quinolone class of drugs use a water-metal ion bridge in interacting with the GyrA subunit of DNA gyrase. Zoliflodacin sits in the same pocket as quinolones but interacts with the GyrB subunit and also stabilizes lethal double-stranded DNA breaks.
View Article and Find Full Text PDFMethods Mol Biol
December 2024
DNA Topology Lab, Molecular Biology Institute of Barcelona (IBMB-CSIC), Barcelona, Spain.
DNA supercoiling in biological systems can occur via three mechanisms. The first is by the activity of DNA topoisomerases, such as DNA gyrases, that can increase or reduce the linking number of relaxed DNA (Lk). The second is via DNA translocation motors, such as RNA and DNA polymerases, that produce twin supercoiled DNA domains: one positively supercoiled in front and one negatively supercoiled behind.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Department of Molecular Microbiology, John Innes Centre, Norwich NR4 7UH, United Kingdom.
Type II topoisomerase DNA gyrase transduces the energy of ATP hydrolysis into the negative supercoiling of DNA. The postulated catalytic mechanism involves stabilization of a chiral DNA loop followed by the passage of the T-segment through the temporarily cleaved G-segment resulting in sign inversion. The molecular basis for this is poorly understood as the chiral loop has never been directly observed.
View Article and Find Full Text PDFFood Chem
February 2025
Department of Biochemistry, Memorial University of Newfoundland, St. John 's, NL, A1C 5S7, Canada. Electronic address:
Powdered samples of guava pulp and processing by-products (single fraction containing crushed seeds, peels, and residual pulp) are rich sources of polyphenols with antidiabetic, anti-obesity, cardioprotective, and anticancer potential. However, post-digestion retention of these bioactivities remains unclear. Therefore, these samples were subjected to in vitro digestion simulating oral, gastric, small intestine, and large intestine phases.
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