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Mature chromatin packing domains persist after RAD21 depletion in 3D.
Sci Adv
January 2025
Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
Understanding chromatin organization requires integrating measurements of genome connectivity and physical structure. It is well established that cohesin is essential for TAD and loop connectivity features in Hi-C, but the corresponding change in physical structure has not been studied using electron microscopy. Pairing chromatin scanning transmission electron tomography with multiomic analysis and single-molecule localization microscopy, we study the role of cohesin in regulating the conformationally defined chromatin nanoscopic packing domains.
View Article and Find Full Text PDFMacromolecular interactions and geometrical confinement determine the 3D diffusion of ribosome-sized particles in live cells.
Proc Natl Acad Sci U S A
January 2025
Department of Chemical Engineering, Stanford University, Stanford, CA 94305.
The crowded bacterial cytoplasm is composed of biomolecules that span several orders of magnitude in size and electrical charge. This complexity has been proposed as the source of the rich spatial organization and apparent anomalous diffusion of intracellular components, although this has not been tested directly. Here, we use biplane microscopy to track the 3D motion of self-assembled bacterial genetically encoded multimeric nanoparticles (bGEMs) with tunable size (20 to 50 nm) and charge (-3,240 to +2,700 e) in live cells.
View Article and Find Full Text PDFRecent advances in biocatalytic and chemoenzymatic synthesis of oligonucleotides.
Chembiochem
January 2025
Institut Pasteur, Department of Structural Biology and Chemistry, 28 Rue du Dr. Roux, 75015, Paris, FRANCE.
Access to synthetic oligonucleotides is crucial for applications in diagnostics, therapeutics, synthetic biology, and nanotechnology. Traditional solid phase synthesis is limited by sequence length and complexities, low yields, high costs and poor sustainability. Similarly, polymerase-based approaches such as in vitro transcription and primer extension reactions do not permit any control on the positioning of modifications and display poor substrate tolerance.
View Article and Find Full Text PDFImpacts of amino acid-linked platinum(II) complexes on DNA structure.
J Biol Inorg Chem
January 2025
Department of Chemistry, Wayne State University, Detroit, MI, USA.
The discovery of cisplatin (cisPt) as an effective anticancer agent was a milestone in the health industry. Despite its success, undesired side effects and acquired resistance still limit the therapeutic usefulness of cisPt. Intrastrand adduct formation at consecutive purines and structural modifications of DNA caused by platinum(II) complexes are important factors for antitumor efficacy.
View Article and Find Full Text PDFPreferential Binding of a Long-Arm Porphyrin Ligand to Higher Order G-Quadruplex under Crowding Conditions.
J Phys Chem B
January 2025
College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
Under conditions that are close to the real cellular environment, the human telomeric single-stranded overhang (∼200 nt) consisting of tens of TTAGGG repeats tends to form higher order structures of multiple G-quadruplex (G4) blocks. On account of the higher biological relevance of higher order G4 structures, ligand compounds binding to higher order G4 are significant for the drug design toward inhibiting telomerase activity. Here, we study the interaction between a cationic porphyrin derivative, 5,10,15,20-tetra{4-[2-(1-methyl-1-piperidinyl)propoxy]phenyl}porphyrin (T4), and a human telomeric G4-dimer (AG(TAG)) in the mimic intracellular molecularly crowded environment (PEG as a crowding agent) and K or Na solution (i.
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