A fraction of the cellular nicking-closing (NC) enzyme cosediments with SV40 chromatin isolated after Triton X-100 treatment of infected cells nuclei. Extraction of viral DNA according to the Hirt procedure by treatment of infected cells with sodium dodecyl sulfate (SDS) followed by sedimentation in sucrose gradient to separate the DNA from the bulk of detergent also revealed NC activity associated with DNA. Reconstitution experiments showed that only prebinding of the NC enzyme to DNA protects it against irreversible inactivation by SDS. These results suggest that a fraction of the cellular NC activity is indeed associated with the viral chromosome in vivo.
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http://dx.doi.org/10.1093/nar/7.3.679 | DOI Listing |
Adv Rheumatol
December 2024
Department of Immunology & Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Soura, Srinagar, Jammu and Kashmir, 190011, India.
Background: As a master immune system regulator, transforming growth factor β1 (TGF-β1) is closely linked to the complicated pathophysiology and development of systemic sclerosis (SSc), a multisystem fibrotic disease.
Objective: We aim to evaluate the transcriptional levels of TGF-β1 mRNA in PBMCs, assess the TGF-β1 serum levels of SSc patients, and compare them with those of healthy subjects.
Methods: PBMCs were isolated from whole blood of 50 SSc patients and in 30 healthy controls.
Cell Rep
December 2024
Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada; Biophysics Department, Faculty of Science, Cairo University, Giza 12613, Egypt. Electronic address:
Uncontrolled degradation and collapse of stalled replication forks (RFs) are primary sources of genomic instability, yet the molecular mechanisms for protecting forks from degradation/collapse remain to be fully elaborated. Here, we show that polynucleotide kinase-phosphatase (PNKP) localizes at stalled forks and protects stalled forks from excessive degradation. The loss of PNKP results in nucleolytic degradation of nascent DNA at stalled RFs.
View Article and Find Full Text PDFEur J Med Chem
February 2025
The First Affiliated Hospital, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. Electronic address:
Evodiamine has been a promising lead structure with broad-spectrum antitumor activity. Druggability optimization is the most challenging part of evodiamine-based lead-to-candidate campaign. Amino acids as building blocks for conjugates are widely incorporated into approved drug and drug candidates, demonstrating highly attractive druggability.
View Article and Find Full Text PDFEur J Med Chem
February 2025
College of Pharmaceutical Sciences, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, Hangzhou, 310014, China. Electronic address:
Addition of fluorine atoms into chemical compounds is a validated strategy to enhance their physical, chemical and biological properties. In this study, FL118, a novel camptothecin-related small molecule known for its unique mechanism of action and superior antitumor efficacy, was utilized as a foundational drug platform. By replacing the hydrogen atom at position 7 of FL118 with a fluoroaryl group, a diverse array of FL118 derivatives were synthesized.
View Article and Find Full Text PDFMolecules
November 2024
Medicinal Chemistry and Drug Discovery Research Centre, Swenam College, 210-6125 Sussex Avenue, Burnaby, BC V5H 4G1, Canada.
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