ArticleNucleic acids research2008
Evidence for an inositol hexakisphosphate-dependent role for Ku in mammalian nonhomologous end joining that is independent of its role in the DNA-dependent protein kinase.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Structural and functional basis of inositol hexaphosphate stimulation of NHEJ through stabilization of Ku-XLF interaction.Nucleic acids research · 2023Article
- Autophosphorylation transforms DNA-PK from protecting to processing DNA ends.Molecular cell · 2022Article
- The Ku complex: recent advances and emerging roles outside of non-homologous end-joining.Cellular and molecular life sciences : CMLS · 2021Review
- The Multifaceted Roles of Ku70/80.International journal of molecular sciences · 2021Review
- Overview of Inositol and Inositol Phosphates on Chemoprevention of Colitis-Induced Carcinogenesis.Molecules (Basel, Switzerland) · 2020Review
- Broad Spectrum Anticancer Activity of Myo-Inositol and Inositol Hexakisphosphate.International journal of endocrinology · 2016Review
- A human short open reading frame (sORF)-encoded polypeptide that stimulates DNA end joining.The Journal of biological chemistry · 2014Article
- A non-catalytic role for inositol 1,3,4,5,6-pentakisphosphate 2-kinase in the synthesis of ribosomal RNA.Journal of cell science · 2013Article
- A role for phosphoinositides in regulating plant nuclear functions.Frontiers in plant science · 2012Article
- Defining signal transduction by inositol phosphates.Sub-cellular biochemistry · 2012Review
- Phytic acid as a potential treatment for alzheimer's pathology: evidence from animal and in vitro models.Journal of Alzheimer's disease : JAD · 2011Article
- Gene deletion of inositol hexakisphosphate kinase 2 predisposes to aerodigestive tract carcinoma.Oncogene · 2009Article
- The flexible and iterative steps within the NHEJ pathway.Progress in biophysics and molecular biologyArticle
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3 authors at 1 institution in 1 country.
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Abstract
Nonhomologous end-joining (NHEJ) is an important pathway for the repair of DNA double-strand breaks (DSBs) and plays a critical role in maintaining genomic stability in mammalian cells. While Ku70/80 (Ku) functions in NHEJ as part of the DNA-dependent protein kinase (DNA-PK), genetic evidence indicates that the role of Ku in NHEJ goes beyond its participation in DNA-PK. Inositol hexakisphosphate (IP(6)) was previously found to stimulate NHEJ in vitro and Ku was identified as an IP(6)-binding factor. Through mutational analysis, we identified a bipartite IP(6)-binding site in Ku and generated IP(6)-binding mutants that ranged from 1.22% to 58.48% of wild-type binding. Significantly, these Ku IP(6)-binding mutants were impaired for participation in NHEJ in vitro and we observed a positive correlation between IP(6) binding and NHEJ. Ku IP(6)-binding mutants were separation-of-function mutants that bound DNA and activated DNA-PK as well as wild-type Ku. Our observations identify a hitherto undefined IP(6)-binding site in Ku and show that this interaction is important for DSB repair by NHEJ in vitro. Moreover, these data indicate that in addition to binding of exposed DNA termini and activation of DNA-PK, the Ku heterodimer plays a role in mammalian NHEJ that is regulated by binding of IP(6).
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