Topoisomerase activities have been measured in nuclear extracts of concanavalin A-stimulated lymphocytes. In parallel with the wave of DNA synthesis, type II topoisomerase activity was considerably increased. After 72 h treatment, this activity was stimulated approx. 20-fold over the activity in untreated cells. In contrast, type I topoisomerase was poorly stimulated after 24 h treatment, and 4-5-fold after 72 h. These findings, together with our previous results on regenerating rat liver, suggest a major role of topoisomerase II in DNA replication.
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http://dx.doi.org/10.1016/0014-5793(84)81212-0 | DOI Listing |
Redox Biol
January 2025
University of Chicago, Department of Molecular Genetics and Cell Biology, 929 E. 57th Street, Chicago, IL, 60637, USA. Electronic address:
During its catalytic cycle, the homodimeric ATPase topoisomerase II alpha (TOP2A) cleaves double stranded DNA and remains covalently bound to 5' ends via tyrosine phosphodiester bonds. After passing a second, intact duplex through, TOP2A rejoins the break and releases from the DNA. Thereby, TOP2A can relieve strain accumulated during transcription, replication and chromatin remodeling and disentangle sister chromatids for mitosis.
View Article and Find Full Text PDFMech Ageing Dev
January 2025
Department of Biological Science, College of Natural Science, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Republic of Korea; BK21 FOUR Education Research Group for Age-Associated Disorder Control Technology, Department of Integrative Biological Science, Chosun University, Gwangju 61452, Republic of Korea; The Basic Science Institute of Chosun University, Chosun University, Gwangju 61452, Republic of Korea. Electronic address:
The protective effects of mangiferin (MAG) against etoposide- and high glucose (HG)-induced DNA damage and aging were investigated in human bone marrow-mesenchymal stem cells (hBM-MSCs). Etoposide, a topoisomerase II inhibitor, was used to induce double-strand breaks (DSBs) in hBM-MSCs, resulting in increased genotoxicity, elevated levels of the DNA damage sensor ATM and CDKN1A, and decreased levels of the aging markers H3 and H4. MAG activated AMPK and SIRT1, thus protecting against DSB-induced damage.
View Article and Find Full Text PDFMol Divers
January 2025
Department of Chemistry, National Institute of Technology Calicut, Kozhikode, 673601, Kerala, India.
Quinoline is a highly privileged scaffold with significant pharmacological potential. Introducing a carbonyl group into the quinoline ring generates a quinolone ring, which exhibits promising biological properties. Incorporating a carboxamide linkage at different positions within the quinoline and quinolone frameworks has proven an effective strategy for enhancing pharmacological properties, particularly anticancer potency.
View Article and Find Full Text PDFMicrobiol Mol Biol Rev
January 2025
Department of Microbiology-Immunology, Northwestern University, Chicago, Illinois, USA.
SUMMARYHuman papillomaviruses (HPVs) are small DNA viruses that are responsible for significant disease burdens worldwide, including cancers of the cervix, anogenital tract, and oropharynx. HPVs infect stratified epithelia at a variety of body locations and link their productive life cycles to the differentiation of the host cell. These viruses have evolved sophisticated mechanisms to exploit cellular pathways, such as DNA damage repair (DDR), to regulate their life cycles.
View Article and Find Full Text PDFCancers (Basel)
January 2025
School of Chemical and Bioprocess Engineering, University College Dublin, D04 V1W8 Dublin, Ireland.
Background/objectives: Despite the numerous advances in glioblastoma multiforme (GBM) treatment, GBM remains as the most malignant and aggressive form of brain cancer, characterized by a very poor outcome, highlighting the ongoing need for the development of new therapeutic strategies. A novel intervention using plasma-assisted local delivery of oncology drugs was developed to mediate the drug delivery, which might improve drug uptake and/or chemotherapeutic action. Topotecan (TPT), a water-soluble topoisomerase I inhibitor with major cytotoxic effects during the S-phase of the cell cycle, was selected as the candidate drug because despite its potent antitumor activity, the systemic administration to the brain is limited due to low crossing of the blood-brain barrier.
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