By moving boundary sedimentation it is shown that the interaction of H1 histone with superhelical circular SV40 DNA results in the formation of giant heterogeneous aggregates. The size of these aggregates grows with increasing H1 concentration. s20,w values of some 10 000 S were measured. As compared with open relaxed circular DNA a preferential interaction of superhelical DNA with H1 histone is observed, irrespective of the sign of the superhelical turns which was reversed by the addition to DNA of ethidium bromide. The addition to the H1 complexed aggregates of ethidium bromide effects a progressive breakdown of the aggregates. Furthermore, the superhelicity of DNA is not changed by the addition of small amounts of H1 histone.
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http://dx.doi.org/10.1093/nar/3.2.419 | DOI Listing |
Nucleic Acids Res
January 2025
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Oscillation of the active form of the initiator protein DnaA (ATP-DnaA) allows for the timely regulation for chromosome replication. After initiation, DnaA-bound ATP is hydrolyzed, producing inactive ADP-DnaA. For the next round of initiation, ADP-DnaA interacts with the chromosomal locus DARS2 bearing binding sites for DnaA, a DNA-bending protein IHF, and a transcription activator Fis.
View Article and Find Full Text PDFJ Biol Chem
December 2024
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address:
Spatial organization of chromatin is essential for cellular functioning. However, the precise mechanisms governing sequence-dependent positioning of nucleosomes on DNA remain unknown in detail. Existing algorithms, considering the sequence-dependent deformability of DNA and its interactions with the histone globular domains, predict rotational setting of only 65% of human nucleosomes mapped in vivo.
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 PDFChembiochem
January 2025
Department of Chemistry, St. Olaf College, 1520 St. Olaf Ave., Northfield, MN, 55057.
O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential, stress-sensing enzyme responsible for adding the O-GlcNAc monosaccharide to thousands of nuclear and cytoplasmic proteins to regulate cellular homeostasis. OGT substrates are found in almost all intracellular processes, and perturbations in protein O-GlcNAc levels have been implicated in proteostatic diseases, such as cancers, metabolic disorders, and neurodegeneration. This broad disease activity makes OGT an attractive therapeutic target; however, the substrate diversity makes pan-inhibition as a therapeutic strategy unfeasible.
View Article and Find Full Text PDFMol Cell
November 2024
Institute of Molecular Biology gGmbH, Ackermannweg 4, 55128 Mainz, Germany; Department of General Biology, Medical School, University of Patras, Rio, Patras 26500 Greece. Electronic address:
Type II topoisomerases (TOP2s) resolve torsional stress accumulated during various cellular processes and are enriched at chromatin loop anchors and topologically associated domain (TAD) boundaries, where, when trapped, can lead to genomic instability promoting the formation of oncogenic fusions. Whether TOP2s relieve topological constraints at these positions and/or participate in 3D chromosome folding remains unclear. Here, we combine 3D genomics, imaging, and GapRUN, a method for the genome-wide profiling of positive supercoiling, to assess the role of TOP2s in shaping chromosome organization in human cells.
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