In trypanosomatids, etiological agents of devastating diseases, replication is robust and finely controlled to maintain genome stability and function in stressful environments. However, these parasites encode several replication protein components and complexes that show potentially variant composition compared with model eukaryotes. This review focuses on the advances made in recent years regarding the differences and peculiarities of the replication machinery in trypanosomatids, including how such divergence might affect DNA replication dynamics and the replication stress response. Comparing the DNA replication machinery and processes of parasites and their hosts may provide a foundation for the identification of targets that can be used in the development of chemotherapies to assist in the eradication of diseases caused by these pathogens.
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http://dx.doi.org/10.1016/j.pt.2017.08.002 | DOI Listing |
Front Immunol
January 2025
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
The innate immune system promptly detects and responds to invading pathogens, with a key role played by the recognition of bacterial-derived DNA through pattern recognition receptors. The Z-DNA binding protein 1 (ZBP1) functions as a DNA sensor inducing type I interferon (IFN) production, innate immune responses and also inflammatory cell death. ZBP1 interacts with cytosolic DNA via its DNA-binding domains, crucial for its activation.
View Article and Find Full Text PDFWorld J Oncol
February 2025
The First Clinical Medical School, Jinan University, Guangzhou 510632, Guangdong, China.
Background: Thymidine kinases (TKs) are key enzymes involved in DNA synthesis and repair, with alterations in their expression associated with various cancers. Thymidine kinase 1 (TK1) and TK2 are cytosolic enzyme proteins that catalyze the addition of a gamma-phosphate group to thymidine. The existing literature on TK1 in cervical squamous cell carcinoma (CESC) fails to address the clinical role of TK1 overexpression and its possible molecular mechanism in CESC.
View Article and Find Full Text PDFiScience
January 2025
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Maintaining metabolic homeostasis requires coordinated nutrient utilization between intracellular organelles and across multiple organ systems. Many organs rely heavily on mitochondria to generate (ATP) from glucose, or stored glycogen. Proteins required for ATP generation are encoded in both nuclear and mitochondrial DNA (mtDNA).
View Article and Find Full Text PDFJ Antimicrob Chemother
January 2025
CH Tourcoing, Service Universitaire des Maladies Infectieuses, 59200 Tourcoing, France.
Introduction: The specificity of HIV-1 DNA genotypic resistance tests (GRTs) is hampered by the detection of the APOBEC-context drug resistance mutations (AC DRMs), usually harboured by replication-incompetent proviruses. We sought factors associated with defective sequences in the HIV-1 pol region. In addition, AC DRMs and their link with defective sequences were investigated.
View Article and Find Full Text PDFJ Med Case Rep
January 2025
Department of Hepatic Biliary Pancreatic Medicine, First Hospital of Jilin University, 1 Xinmin Avenue, Changchun, 130021, China.
Background: Dyskeratosis congenita is a rare genetic disease due to telomere biology disorder and characterized by heterogeneous clinical manifestations and severe complications. "Porto-sinusoidal vascular disease" has been recently proposed, according to new diagnostic criteria, to replace the term "idiopathic non-cirrhotic portal hypertension." TERT plays an important role in telomeric DNA repair and replication.
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