ArticleMolecular and cellular biology2007
The DNA-dependent protein kinase catalytic subunit is phosphorylated in vivo on threonine 3950, a highly conserved amino acid in the protein kinase domain.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 123 citations in OpenAlex.
- Enhanced ETS1 stability by DNAPKcs orchestrates transcriptional changes during chemoresistance in triple negative breast cancer.NPJ breast cancer · 2025Article
- Photodynamic Therapy and Dietary Antioxidants: A Dual Strategy for Genome Stability and DNA Damage Repair.Cancer medicine · 2025Review
- DNA-PK: A synopsis beyond synapsis.DNA repair · 2024Review
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- Kaposi's sarcoma herpesvirus exploits the DNA damage response to circularize its genome.Nucleic acids research · 2024Article
- Structure and function of the apical PIKKs in double-strand break repair.Current opinion in structural biology · 2023Review
- Human DNA-dependent protein kinase activation mechanism.Nature structural & molecular biology · 2023Article
- Physical ARTEMIS:DNA-PKcs interaction is necessary for V(D)J recombination.Nucleic acids research · 2022Article
- DNA-PKcs: A Targetable Protumorigenic Protein Kinase.Cancer research · 2022Review
- Article
- 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
- Stages, scaffolds and strings in the spatial organisation of non-homologous end joining: Insights from X-ray diffraction and Cryo-EM.Progress in biophysics and molecular biology · 2021Article
- Visualizing functional dynamicity in the DNA-dependent protein kinase holoenzyme DNA-PK complex by integrating SAXS with cryo-EM.Progress in biophysics and molecular biology · 2021Article
- Uncovering DNA-PKcs ancient phylogeny, unique sequence motifs and insights for human disease.Progress in biophysics and molecular biology · 2021Article
- Repair of DNA Double-Strand Breaks by the Nonhomologous End Joining Pathway.Annual review of biochemistry · 2021Review
- Molecular regulation of lifespan extension in fertile ant workers.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2021Article
- Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity.Nucleic acids research · 2021Article
- Structure of an activated DNA-PK and its implications for NHEJ.Molecular cell · 2021Article
- Structural insights into the role of DNA-PK as a master regulator in NHEJ.Genome instability & disease · 2021Review
- Deciphering the role of distinct DNA-PK phosphorylations at collapsed replication forks.DNA repair · 2020Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
The protein kinase activity of the DNA-dependent protein kinase (DNA-PK) is required for the repair of DNA double-strand breaks (DSBs) via the process of nonhomologous end joining (NHEJ). However, to date, the only target shown to be functionally relevant for the enzymatic role of DNA-PK in NHEJ is the large catalytic subunit DNA-PKcs itself. In vitro, autophosphorylation of DNA-PKcs induces kinase inactivation and dissociation of DNA-PKcs from the DNA end-binding component Ku70/Ku80. Phosphorylation within the two previously identified clusters of phosphorylation sites does not mediate inactivation of the assembled complex and only partially regulates kinase disassembly, suggesting that additional autophosphorylation sites may be important for DNA-PK function. Here, we show that DNA-PKcs contains a highly conserved amino acid (threonine 3950) in a region similar to the activation loop or t-loop found in the protein kinase domain of members of the typical eukaryotic protein kinase family. We demonstrate that threonine 3950 is an in vitro autophosphorylation site and that this residue, as well as other previously identified sites in the ABCDE cluster, is phosphorylated in vivo in irradiated cells. Moreover, we show that mutation of threonine 3950 to the phosphomimic aspartic acid abrogates V(D)J recombination and leads to radiation sensitivity. Together, these data suggest that threonine 3950 is a functionally important, DNA damage-inducible phosphorylation site and that phosphorylation of this site regulates the activity of DNA-PKcs.
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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.