ArticleNature structural & molecular biology2023
Human DNA-dependent protein kinase activation mechanism.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed, 25 citations in OpenAlex.
- PTK7 scaffolds DNA-PKcs to promote DNA damage response and immune evasion in triple-negative breast cancer.Oncogene · 2026Article
- A novel combination approach targeting P300 and DNA-PK exploits epigenetic dependencies in acute myeloid leukemia.Molecular therapy. Oncology · 2026Article
- A multispecies toolkit ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Tel1-Rad9 axis links DNA double-strand break end-tethering to repair pathway choice.Nucleic acids research · 2026Article
- Targeting DNA-PK: medicinal chemistry insights into small-molecule inhibitor discovery and optimisation.RSC medicinal chemistry · 2026Review
- Deciphering the Ubiquitin-like Code of DNA-PK: Mechanisms and Therapeutic Opportunities.Biomolecules · 2026Review
- Multi-scale in-silico modelling to unveil structural requirements for DNA-PK inhibitors as radiosensitizers and MolSHAP based design of novel ligands.Journal of computer-aided molecular design · 2025Article
- Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Article
- Computational study of terahertz-driven controllable molecular isomerization.Nature communications · 2025Article
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- Making PI3K superfamily enzymes run faster.Advances in biological regulation · 2025Review
- Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1.bioRxiv : the preprint server for biology · 2024Article
- ER-associated degradation ligase HRD1 links ER stress to DNA damage repair by modulating the activity of DNA-PKcs.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- DNA-PK: A synopsis beyond synapsis.DNA repair · 2024Review
- Identification of 6-Anilino Imidazo[4,5-Journal of medicinal chemistry · 2024Article
- Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024Review
- Unravelling the complexities of DNA-PK activation by structure-based mutagenesis.Research square · 2023Article
- Structure and function of the apical PIKKs in double-strand break repair.Current opinion in structural biology · 2023Review
- Structure and mechanism in non-homologous end joining.DNA repair · 2023Article
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), a multicomponent complex including the DNA-PK catalytic subunit and Ku70/80 heterodimer together with DNA, is central to human DNA damage response and repair. Using a DNA-PK-selective inhibitor (M3814), we identified from one dataset two cryo-EM structures of the human DNA-PK complex in different states, the intermediate state and the active state. Here we show that activation of the kinase is regulated through conformational changes caused by the binding ligand and the string region (residues 802-846) of the DNA-PK catalytic subunit, particularly the helix-hairpin-helix motif (residues 816-836) that interacts with DNA. These observations demonstrate the regulatory role of the ligand and explain why DNA-PK is DNA dependent. Cooperation and coordination among binding partners, disordered flexible regions and mechanically flexible HEAT repeats modulate the activation of the kinase. Together with previous findings, these results provide a better molecular understanding of DNA-PK catalysis.
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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.