The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
DNA-PK: at the cross-roads of biochemistry and genetics
Open accessAbstract
Silver nanoparticles (Ag-np) were reported to be toxic to eukaryotic cells. These potentially detrimental effects of Ag-np can be advantageous in experimental therapeutics. They are currently being employed to enhance the therapeutic efficacy of cancer drugs. In this study, we demonstrate that Ag-np treatment trigger the activation of DNA-PKcs and JNK pathway at selected doses, presumably as a physiologic response to DNA damage and repair in normal and malignant cells. Ag-np altered the telomere dynamics by disrupting the shelterin complex located at the telomeres and telomere lengths. The genotoxic effect of Ag-np was not restricted to telomeres but the entire genome as Ag-np induced γ-H2AX foci formation, an indicator of global DNA damage. Inhibition of DNA-PKcs activity sensitised the cancer cells towards the cytotoxicity of Ag-np and substantiated the damaging effect of Ag-np at telomeres in human cancer cells. Abrogation of JNK mediated DNA repair and extensive damage of telomeres led to greater cell death following Ag-np treatment in DNA-PKcs inhibited cancer cells. Collectively, this study suggests that improved anti-proliferative and cytotoxic effects of Ag-np treatment in cancer cells can be achieved by the inhibition of DNA-PKcs.
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Cites
A Single Ataxia Telangiectasia Gene with a Product Similar to PI-3 Kinase
Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Tagle, D. A., Smith, S., Uziel, T., Sfez, S., et al. (1995) · Science · doi:10.1126/science.7792600 · Cited by 2,785
Morrow, D. M., Tagle, D. A., Shiloh, Y., Collins, F. S., & Hieter, P. (1995) · Cell · doi:10.1016/0092-8674(95)90480-8 · Cited by 370
Studies on mammalian mutants defective in rejoining double-strand breaks in DNA
Jeggo, P. A. (1990) · Mutation Research/Reviews in Genetic Toxicology · doi:10.1016/0165-1110(90)90028-a · Cited by 171
Self-citation
Cited by
Takata, M., Sasaki, M. S., Sonoda, E., Morrison, C., Hashimoto, M., Utsumi, H., Yamaguchi‐Iwai, Y., Shinohara, A., & Takeda, S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.18.5497 · Cited by 1,229
DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer
Huang, R.-X., & Zhou, P.-K. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0150-x · Cited by 1,198
Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mre11/Rad50 complex
Paull, T. T., & Gellert, M. (1999) · Genes & Development · doi:10.1101/gad.13.10.1276 · Cited by 551
Shao, R.-G. (1999) · The EMBO Journal · doi:10.1093/emboj/18.5.1397 · Cited by 344
Enzymatic Processing of Radiation-Induced Free Radical Damage in DNA
Wallace, S. S. (1998) · Radiation Research · doi:10.2307/3579809 · Cited by 334
Metadata
- Authors
- Jeggo, P. A.
- Venue
- Mutation Research/DNA Repair
- Publisher
- Elsevier BV
- Published
- 1997-06
- Volume
- 384
- Issue
- 1
- Pages
- 1-14
- ISSN
- 0921-8777 (ISSN-L)
- OpenAlex
- W2058664192
- Cited by
- 166
- References
- 3
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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