ArticleMolecular and cellular biology2003
Autophosphorylation of the catalytic subunit of the DNA-dependent protein kinase is required for efficient end processing during DNA double-strand break repair.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers.
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Who cites it
177 citing papers in PubMed, 321 citations in OpenAlex.
- Translational control by RPL22L1-specific ribosomes enhances DNA repair and chemoresistance.Nature communications · 2026Article
- 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
- Single-molecule imaging reveals the kinetics of non-homologous end-joining in living cells.Nature communications · 2024Article
- Targeting the DNA damage response in cancer.MedComm · 2024Review
- DNA-PK: A synopsis beyond synapsis.DNA repair · 2024Review
- Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024Review
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- Single-molecule imaging reveals the kinetics of non-homologous end-joining in living cells.bioRxiv : the preprint server for biology · 2024Article
- DNA-PK controls Apollo's access to leading-end telomeres.Nucleic acids research · 2024Article
- Automating data analysis for hydrogen/deuterium exchange mass spectrometry using data-independent acquisition methodology.Nature communications · 2024Article
- Structural role for DNA Ligase IV in promoting the fidelity of non-homologous end joining.Nature communications · 2024Article
- IN-DEPTH MAPPING OF DNA-PKcs SIGNALING UNCOVERS CONSERVED FEATURES OF ITS KINASE SPECIFICITY.bioRxiv : the preprint server for biology · 2024Article
- Unravelling the complexities of DNA-PK activation by structure-based mutagenesis.Research square · 2023Article
- How to fix DNA breaks: new insights into the mechanism of non-homologous end joining.Biochemical Society transactions · 2023Review
- Structure and function of the apical PIKKs in double-strand break repair.Current opinion in structural biology · 2023Review
- Review
- Structure and mechanism in non-homologous end joining.DNA repair · 2023Article
- Genome-wide analysis of DNA-PK-bound MRN cleavage products supports a sequential model of DSB repair pathway choice.Nature communications · 2023Article
- Discovery and Characterization of ZL-2201, a Potent, Highly Selective, and Orally Bioavailable Small-molecule DNA-PK Inhibitor.Cancer research communications · 2023Article
- DNA-PK is activated by SIRT2 deacetylation to promote DNA double-strand break repair by non-homologous end joining.Nucleic acids research · 2023Article
117 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
The DNA-dependent protein kinase (DNA-PK) plays an essential role in nonhomologous DNA end joining (NHEJ) by initially recognizing and binding to DNA breaks. We have shown that in vitro, purified DNA-PK undergoes autophosphorylation, resulting in loss of activity and disassembly of the kinase complex. Thus, we have suggested that autophosphorylation of the DNA-PK catalytic subunit (DNA-PKcs) may be critical for subsequent steps in DNA repair. Recently, we defined seven autophosphorylation sites within DNA-PKcs. Six of these are tightly clustered within 38 residues of the 4,127-residue protein. Here, we show that while phosphorylation at any single site within the major cluster is not critical for DNA-PK's function in vivo, mutation of several sites abolishes the ability of DNA-PK to function in NHEJ. This is not due to general defects in DNA-PK activity, as studies of the mutant protein indicate that its kinase activity and ability to form a complex with DNA-bound Ku remain largely unchanged. However, analysis of rare coding joints and ends demonstrates that nucleolytic end processing is dramatically reduced in joints mediated by the mutant DNA-PKcs. We therefore suggest that autophosphorylation within the major cluster mediates a conformational change in the DNA-PK complex that is critical for DNA end processing. However, autophosphorylation at these sites may not be sufficient for kinase disassembly.
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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.