ArticleNucleic acids research2004
Visualization of inositol phosphate-dependent mobility of Ku: depletion of the DNA-PK cofactor InsP6 inhibits Ku mobility.
Article in Nucleic acids research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Improving homology-directed repair by small molecule agents for genetic engineering in unconventional yeast?-Learning from the engineering of mammalian systems.Microbial biotechnology · 2024Review
- The Proteasome Activator PA200/PSME4: An Emerging New Player in Health and Disease.Biomolecules · 2022Review
- The Ku complex: recent advances and emerging roles outside of non-homologous end-joining.Cellular and molecular life sciences : CMLS · 2021Review
- Overview of Inositol and Inositol Phosphates on Chemoprevention of Colitis-Induced Carcinogenesis.Molecules (Basel, Switzerland) · 2020Review
- Role of Inositols and Inositol Phosphates in Energy Metabolism.Molecules (Basel, Switzerland) · 2020Review
- Inositol hexakisphosphate increases the size of platelet aggregates.Biochemical pharmacology · 2019Article
- Control of gene editing by manipulation of DNA repair mechanisms.Mammalian genome : official journal of the International Mammalian Genome Society · 2017Review
- The crystal structure of mammalian inositol 1,3,4,5,6-pentakisphosphate 2-kinase reveals a new zinc-binding site and key features for protein function.The Journal of biological chemistry · 2017Article
- Chemical Inhibitors of Non-Homologous End Joining Increase Targeted Construct Integration in Cryptococcus neoformans.PloS one · 2016Article
- Broad Spectrum Anticancer Activity of Myo-Inositol and Inositol Hexakisphosphate.International journal of endocrinology · 2016Review
- The wavy Mutation Maps to the Inositol 1,4,5-Trisphosphate 3-Kinase 2 (IP3K2) Gene of Drosophila and Interacts with IP3R to Affect Wing Development.G3 (Bethesda, Md.) · 2015Article
- SMAR1 coordinates HDAC6-induced deacetylation of Ku70 and dictates cell fate upon irradiation.Cell death & disease · 2014Article
- Induction of H2AX phosphorylation in tumor cells by gossypol acetic acid is mediated by phosphatidylinositol 3-kinase (PI3K) family.Cancer cell international · 2014Article
- A role for phosphoinositides in regulating plant nuclear functions.Frontiers in plant science · 2012Article
- Mutant huntingtin impairs Ku70-mediated DNA repair.The Journal of cell biology · 2010Article
- Gene deletion of inositol hexakisphosphate kinase 2 predisposes to aerodigestive tract carcinoma.Oncogene · 2009Article
- Activation Mechanism of Protein Kinase B by DNA-dependent Protein Kinase Involved in the DNA Repair System.Toxicological research · 2008Article
- Review
- Intracellular localization of human Ins(1,3,4,5,6)P5 2-kinase.The Biochemical journal · 2007Article
- Effect of inositol hexakisphosphate kinase 2 on transforming growth factor beta-activated kinase 1 and NF-kappaB activation.The Journal of biological chemistry · 2007Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Repair of DNA double-strand breaks (DSBs) in mammalian cells by nonhomologous end-joining (NHEJ) is initiated by the DNA-PK protein complex. Recent studies have shown inositol hexakisphosphate (InsP6) is a potent cofactor for DNA-PK activity in NHEJ. Specifically, InsP6 binds to the Ku component of DNA-PK, where it induces a conformational change and a corresponding increase in DNA end-joining activity. However, the effect of InsP6 on the dynamics of Ku, such as its mobility in the nucleus, is unknown. Importantly, these dynamics reflect the character of Ku's interactions with other molecules. To address this question, the diffusion of Ku was measured by fluorescence photobleaching experiments using cells expressing green fluorescent protein (GFP)-labeled Ku. InsP6 was depleted by treating cells with calmodulin inhibitors, which included the compounds W7 and chlorpromazine. These treatments caused a 50% reduction in the mobile fraction of Ku-GFP, and this could be reversed by replenishing cells with InsP6. By expressing deletion mutants of Ku-GFP, it was determined that its W7-sensitive region occurred at the N-terminus of the dimerization domain of Ku70. These results therefore show that InsP6 enhances Ku mobility through a discrete region of Ku70, and modulation of InsP6 levels in cells represents a potential avenue for regulating NHEJ by affecting the dynamics of Ku and hence its interaction with other nuclear proteins.
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Registered trials
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.