Topoisomerase III (topo III), a type IA topoisomerase, is widespread in hyperthermophilic archaea. In order to interrogate the in vivo role of archaeal topo III, we constructed and characterized a topo III gene deletion mutant of Sulfolobus islandicus. The mutant was viable but grew more slowly than the wild-type strain, especially in a nutrient-poor medium. Flow cytometry analysis revealed changes of the mutant in growth cycle characteristics including an increase in proportion of cells containing either more than two genome equivalents or less than one genome equivalent in exponentially-growing cultures. As shown by fluorescence microscopy, a fraction of mutant cells in the cultures were drastically enlarged, and at least some of the enlarged cells were apparently capable of resuming cell division. The mutant also shows a different transcriptional profile from that of the wild-type strain. Our results suggest that the enzyme may serve roles in chromosomal segregation and control of the level of supercoiling in the cell.
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http://dx.doi.org/10.1016/j.jgg.2011.05.001 | 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 PDFMolecules
November 2024
Medicinal Chemistry and Drug Discovery Research Centre, Swenam College, 210-6125 Sussex Avenue, Burnaby, BC V5H 4G1, Canada.
Int J Mol Sci
November 2024
Biomolecular Sciences Institute, Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA.
Tuberculosis (TB) caused by is a leading infectious cause of death globally. The treatment of patients becomes much more difficult for the increasingly common multi-drug resistant TB. Topoisomerase I is essential for the viability of and has been validated as a new target for the discovery of novel treatment against TB resistant to the currently available drugs.
View Article and Find Full Text PDFJ Control Release
January 2025
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & Center for Molecular Imaging and Translational Medicine, School of Public Health, Shenzhen Research Institute of Xiamen University, Xiamen University, Xiamen 361102, China. Electronic address:
Camptothecin (CPT) and podophyllotoxin (PPT) function as topoisomerase (TOP) I and tubulin inhibitors, respectively, with potent anticancer effects in a variety of cancers. Despite its promise, the clinical applicability of the combination of CPT and PPT faces challenges, including potential side effect and limited therapeutic efficacy. In this study, we designed co-assembly nanomedicines with the different weight (w/w) ratios of amphiphilic Evans blue conjugated CPT prodrug (EB-ss-CPT) and PPT molecules, denoted as ECT Nano.
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