DNA-dependent protein kinase (DNA-PK), a member of phosphatidylinositol-kinase family, is a key protein in mammalian DNA double-strand break (DSB) repair that helps to maintain genomic integrity. DNA-PK also plays a central role in immune cell development and protects telomerase during cellular aging. Epigenetic deregulation due to endogenous and exogenous factors may affect the normal function of DNA-PK, which in turn could impair DNA repair and contribute to genomic instability. Recent studies implicate a role for epigenetics in the regulation of DNA-PK expression in normal and cancer cells, which may impact cancer progression and metastasis as well as provide opportunities for treatment and use of DNA-PK as a novel cancer biomarker. In addition, several small molecules and biological agents have been recently identified that can inhibit DNA-PK function or expression, and thus hold promise for cancer treatments. This review discusses the impact of epigenetic alterations and the expression of DNA-PK in relation to the DNA repair mechanisms with a focus on its differential levels in normal and cancer cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.mrrev.2018.06.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sequence and biochemical analysis of vaccinia virus A32 protein: Implications for in vitro stability and coiled-coil motif mediated regulation of the DNA-dependent ATPase activity.
PLoS One
January 2025
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
Nucleocytoplasmic large DNA viruses (NCLDVs) have massive genome and particle sizes compared to other known viruses. NCLDVs, including poxviruses, encode ATPases of the FtsK/HerA superfamily to facilitate genome encapsidation. However, their biochemical and structural characteristics are yet to be discerned.
View Article and Find Full Text PDFTargeted knockdown of ATM, ATR, and PDEδ increases Gag HIV-1 VLP production in HEK293 cells.
Appl Microbiol Biotechnol
January 2025
Grup d'Enginyeria de Bioprocessos i Biocatàlisi Aplicada, ENG4BIO, Escola d'Enginyeria, Universitat Autònoma de Barcelona, Campus de Bellaterra, Cerdanyola del Vallès, 08193, Barcelona, Spain.
Several strategies have been developed in recent years to improve virus-like particle (VLP)-based vaccine production processes. Among these, the metabolic engineering of cell lines has been one of the most promising approaches. Based on previous work and a proteomic analysis of HEK293 cells producing Human Immunodeficiency Virus-1 (HIV-1) Gag VLPs under transient transfection, four proteins susceptible of enhancing VLP production were identified: ataxia telangiectasia mutated (ATM), ataxia telangiectasia and rad3-related (ATR), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta (PDEδ).
View Article and Find Full Text PDFSPRTN metalloprotease participates in repair of ROS-mediated DNA-protein crosslinks.
Sci Rep
December 2024
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA.
Exposure to reactive oxygen species (ROS) can induce DNA-protein crosslinks (DPCs), unusually bulky DNA lesions that block replication and transcription and play a role in aging, cancer, cardiovascular disease, and neurodegenerative disorders. Repair of DPCs depends on the coordinated efforts of proteases and DNA repair enzymes to cleave the protein component of the lesion to smaller DNA-peptide crosslinks which can be processed by tyrosyl-DNA phosphodiesterases 1 and 2, nucleotide excision and homologous recombination repair pathways. DNA-dependent metalloprotease SPRTN plays a role in DPC repair, and SPRTN-deficient mice exhibit an accelerated aging phenotype and develop liver cancer early in life.
View Article and Find Full Text PDFExtracellular Mitochondria Exacerbate Retinal Pigment Epithelium Degeneration in Diabetic Retinopathy.
Diabetes
December 2024
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Advances in fundus imaging are revealing disruptions in the neurovascular unit in diabetic retinopathy (DR). In the era of anti-VEGF treatment, a thorough characterization of neurodegeneration is imperative until DR patients are sufficiently cured. Here we demonstrate that extracellular mitochondria exacerbate retinal pigment epithelium (RPE) degeneration and inflammation in DR.
View Article and Find Full Text PDFDNA Ligase I Circularises Potato Spindle Tuber Viroid RNA in a Biomolecular Condensate.
Mol Plant Pathol
December 2024
Plant Molecular and Cell Biology Program, University of Florida, Gainesville, Florida, USA.
Viroids are single-stranded circular noncoding RNAs that mainly infect crops. Upon infection, nuclear-replicating viroids engage host DNA-dependent RNA polymerase II for RNA-templated transcription, which is facilitated by a host protein TFIIIA-7ZF. The sense-strand and minus-strand RNA intermediates are differentially localised to the nucleolus and nucleoplasm regions, respectively.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!