ArticleMolecular cell2021
Structure of an activated DNA-PK and its implications for NHEJ.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed.
- PTK7 scaffolds DNA-PKcs to promote DNA damage response and immune evasion in triple-negative breast cancer.Oncogene · 2026Article
- The Advantages of AI for Computational Protein Studies and Looking Ahead at the Next Challenges: Single Structures Are Not Enough.Journal of molecular biology · 2026Review
- Core NHEJ Factors Maintain Synapsis Across Diverse DNA End Structures.bioRxiv : the preprint server for biology · 2026Article
- End processing in NHEJ by Polymerase λ and PNKP is coordinated during short-range synapsis.Nature communications · 2026Article
- DNA-PK driven nucleosome unwrapping enables NHEJ in chromatin.Nature communications · 2026Article
- Structural mechanism of TOPBP1 activating the ATR-ATRIP replication checkpoint kinase.Nature structural & molecular biology · 2026Article
- Ku70-SAP domain has an overlapping function with DNA-PKcs in limiting the lateral movement of the Ku ring along DNA.Nucleic acids research · 2026Article
- Huntingtin (HTT) interactome in regulation of DNA repair/remodeling and RNA processing pathways.Life science alliance · 2026Article
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- DNA-PK-mediated CRTC2 phosphorylation promotes NHEJ and suppresses antitumor immunity via relocation to repair complexes.Nature communications · 2026Article
- Interdependent roles of BRCA1, CtBP, estrogen, and NADH/NAD+ ratio in error-prone repair, breast cancer initiation, and metastasis.Molecular biology reports · 2026Review
- Nonhomologous end joining-the importance of end tethering and beyond.Genes & development · 2026Review
- Efficient sampling of large-scale transition pathways and intermediate conformations in sub-mesoscopic protein complexes.Nature communications · 2026Article
- Structure of Bacillus subtilis Ku-mediated DNA synaptic complex.Nucleic acids research · 2026Article
- Targeting DNA repair mechanisms in cancer therapy: the role of small molecule DNA repair inhibitors.NAR cancer · 2025Review
- DNASE1L3 surveils mitochondrial DNA on the surface of distinct mammalian cells.bioRxiv : the preprint server for biology · 2025Article
- CIAA: Integrated Proteomics and Structural Modeling for Understanding Cysteine Reactivity with Iodoacetamide Alkyne.ACS chemical biology · 2025Article
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- Senataxin and DNA-PKcs redundantly promote non-homologous end joining repair of DNA double strand breaks during V(D)J recombination.Science advances · 2025Article
38 more citing papers are in PubMed but not listed here.
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10 authors.
Funding
Abstract
DNA-dependent protein kinase (DNA-PK), like all phosphatidylinositol 3-kinase-related kinases (PIKKs), is composed of conserved FAT and kinase domains (FATKINs) along with solenoid structures made of HEAT repeats. These kinases are activated in response to cellular stress signals, but the mechanisms governing activation and regulation remain unresolved. For DNA-PK, all existing structures represent inactive states with resolution limited to 4.3 Å at best. Here, we report the cryoelectron microscopy (cryo-EM) structures of DNA-PKcs (DNA-PK catalytic subunit) bound to a DNA end or complexed with Ku70/80 and DNA in both inactive and activated forms at resolutions of 3.7 Å overall and 3.2 Å for FATKINs. These structures reveal the sequential transition of DNA-PK from inactive to activated forms. Most notably, activation of the kinase involves previously unknown stretching and twisting within individual solenoid segments and loosens DNA-end binding. This unprecedented structural plasticity of helical repeats may be a general regulatory mechanism of HEAT-repeat proteins.
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