ArticleNucleic acids research2008
A mechanism for DNA-PK activation requiring unique contributions from each strand of a DNA terminus and implications for microhomology-mediated nonhomologous DNA end joining.
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 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- ERCC6L2 ensures repair fidelity for staggered-end DNA double-strand breaks.Nature communications · 2026Article
- Design, synthesis, and structure-activity relationship studies of 4-substituted phenylpyrazolidinone derivatives as potent Ku70/80 targeted DNA-PK inhibitors.RSC medicinal chemistry · 2025Article
- CRISPR-Cas9-mediated homology-directed repair for precise gene editing.Molecular therapy. Nucleic acids · 2024Review
- Polymorphisms of DNA Repair Genes in Thyroid Cancer.International journal of molecular sciences · 2024Review
- Advance trends in targeting homology-directed repair for accurate gene editing: An inclusive review of small molecules and modified CRISPR-Cas9 systems.BioImpacts : BI · 2022Review
- Recent Advances in the Development of Non-PIKKs Targeting Small Molecule Inhibitors of DNA Double-Strand Break Repair.Frontiers in oncology · 2022Review
- X-ray scattering reveals disordered linkers and dynamic interfaces in complexes and mechanisms for DNA double-strand break repair impacting cell and cancer biology.Protein science : a publication of the Protein Society · 2021Review
- Cryo-EM of NHEJ supercomplexes provides insights into DNA repair.Molecular cell · 2021Article
- Discovery and development of novel DNA-PK inhibitors by targeting the unique Ku-DNA interaction.Nucleic acids research · 2020Article
- Activation of DNA-PK by hairpinned DNA ends reveals a stepwise mechanism of kinase activation.Nucleic acids research · 2020Article
- Cryo-EM structure of human DNA-PK holoenzyme.Cell research · 2017Article
- DNA requirements for interaction of the C-terminal region of Ku80 with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs).DNA repair · 2017Article
- Overhang polarity of chromosomal double-strand breaks impacts kinetics and fidelity of yeast non-homologous end joining.Nucleic acids research · 2016Article
- Single-stranded DNA oligomers stimulate error-prone alternative repair of DNA double-strand breaks through hijacking Ku protein.Nucleic acids research · 2015Article
- Preventing Damage Limitation: Targeting DNA-PKcs and DNA Double-Strand Break Repair Pathways for Ovarian Cancer Therapy.Frontiers in oncology · 2015Review
- Recognition of DNA Termini by the C-Terminal Region of the Ku80 and the DNA-Dependent Protein Kinase Catalytic Subunit.PloS one · 2015Article
- Structure of the herpes simplex virus 1 genome: manipulation of nicks and gaps can abrogate infectivity and alter the cellular DNA damage response.Journal of virology · 2014Article
- Chemotherapy induced DNA damage response: convergence of drugs and pathways.Cancer biology & therapy · 2013Review
- Repair of double-strand breaks by end joining.Cold Spring Harbor perspectives in biology · 2013Review
- Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis.International journal of molecular sciences · 2012Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
DNA-dependent protein kinase (DNA-PK) is an essential component of the nonhomologous end joining pathway (NHEJ), responsible for the repair of DNA double-strand breaks. Ku binds a DSB and recruits the catalytic subunit, DNA-PKcs, where it is activated once the kinase is bound to the DSB. The precise mechanism by which DNA activates DNA-PK remains unknown. We have investigated the effect of DNA structure on DNA-PK activation and results demonstrate that in Ku-dependent DNA-PKcs reactions, DNA-PK activation with DNA effectors containing two unannealed ends was identical to activation observed with fully duplex DNA effectors of the same length. The presence of a 6-base single-stranded extension resulted in decreased activation compared to the fully duplex DNA. DNA-PK activation using DNA effectors with compatible termini displayed increased activity compared to effectors with noncompatible termini. A strand orientation preference was observed in these reactions and suggests a model where the 3' strand of the terminus is responsible for annealing and the 5' strand is involved in activation of DNA-PK. These results demonstrate the influence of DNA structure and orientation on DNA-PK activation and provide a molecular mechanism of activation resulting from compatible termini, an essential step in microhomology-mediated NHEJ.
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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.