ArticleFree radical biology & medicine2010
DNA-PKcs deficiency leads to persistence of oxidatively induced clustered DNA lesions in human tumor cells.
Article in Free radical biology & medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 69 citations in OpenAlex.
- DNA-PKcs and PARP1 at the interface between DNA damage responses and cGAS-STING signaling: context-dependent roles and therapeutic implications.Cancer biology & therapy · 2026Review
- Clustered DNA Damage Patterns after Proton Therapy Beam Irradiation Using Plasmid DNA.International journal of molecular sciences · 2022Article
- The DNA Double-Strand Break Repair in Glioma: Molecular Players and Therapeutic Strategies.Molecular neurobiology · 2022Review
- DNA-PKcs: A Targetable Protumorigenic Protein Kinase.Cancer research · 2022Review
- DNA repair protein DNA-PK protects PC12 cells from oxidative stress-induced apoptosis involving AKT phosphorylation.Molecular biology reports · 2022Article
- Reparative properties of human glioblastoma cells after single exposure to a wide range of X-ray doses.Frontiers in oncology · 2022Article
- DNA damage repair in glioblastoma: current perspectives on its role in tumour progression, treatment resistance and PIKKing potential therapeutic targets.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Review
- Article
- DNA-PKcs modulates progenitor cell proliferation and fibroblast senescence in idiopathic pulmonary fibrosis.BMC pulmonary medicine · 2019Article
- Differences in vector-genome processing and illegitimate integration of non-integrating lentiviral vectors.Gene therapy · 2017Article
- Rapid Diminution in the Level and Activity of DNA-Dependent Protein Kinase in Cancer Cells by a Reactive Nitro-Benzoxadiazole Compound.International journal of molecular sciences · 2016Article
- DNA repair targeted therapy: The past or future of cancer treatment?Pharmacology & therapeutics · 2016Review
- DNA-PKcs deficiency sensitizes the human hepatoma HepG2 cells to cisplatin and 5-fluorouracil through suppression of the PI3K/Akt/NF-κB pathway.Molecular and cellular biochemistry · 2015Article
- Preventing Damage Limitation: Targeting DNA-PKcs and DNA Double-Strand Break Repair Pathways for Ovarian Cancer Therapy.Frontiers in oncology · 2015Review
- The catalytic subunit of DNA-dependent protein kinase is required for cellular resistance to oxidative stress independent of DNA double-strand break repair.Free radical biology & medicine · 2014Article
- Chemotherapeutic compounds targeting the DNA double-strand break repair pathways: the good, the bad, and the promising.Frontiers in oncology · 2014Review
- Analysis of telomere length and function in radiosensitive mouse and human cells in response to DNA-PKcs inhibition.Genome integrity · 2013Article
- Small Molecules, Inhibitors of DNA-PK, Targeting DNA Repair, and Beyond.Frontiers in pharmacology · 2013Article
- Damage clusters after gamma irradiation of a nanoparticulate plasmid DNA peptide condensate.Radiation and environmental biophysics · 2012Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
DNA-dependent protein kinase (DNA-PK) is a key non-homologous-end-joining (NHEJ) nuclear serine/threonine protein kinase involved in various DNA metabolic and damage signaling pathways contributing to the maintenance of genomic stability and prevention of cancer. To examine the role of DNA-PK in processing of non-DSB clustered DNA damage, we have used three models of DNA-PK deficiency, i.e., chemical inactivation of its kinase activity by the novel inhibitors IC86621 and NU7026, knockdown and complete absence of the protein in human breast cancer (MCF-7) and glioblastoma cell lines (MO59-J/K). A compromised DNA-PK repair pathway led to the accumulation of clustered DNA lesions induced by gamma-rays. Tumor cells lacking protein expression or with inhibited kinase activity showed a marked decrease in their ability to process oxidatively induced non-DSB clustered DNA lesions measured using a modified version of pulsed-field gel electrophoresis or single-cell gel electrophoresis (comet assay). In all cases, DNA-PK inactivation led to a higher level of lesion persistence even after 24-72h of repair. We suggest a model in which DNA-PK deficiency affects the processing of these clusters first by compromising base excision repair and second by the presence of catalytically inactive DNA-PK inhibiting the efficient processing of these lesions owing to the failure of DNA-PK to disassociate from the DNA ends. The information rendered will be important for understanding not only cancer etiology in the presence of an NHEJ deficiency but also cancer treatments based on the induction of oxidative stress and inhibition of cluster repair.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.