ArticleThe Journal of biological chemistry2013
DNA-dependent protein kinase regulates DNA end resection in concert with Mre11-Rad50-Nbs1 (MRN) and ataxia telangiectasia-mutated (ATM).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- BUB1 and CDK4/6 Dual Inhibition Increases Radiation Sensitivity in Glioblastoma, Lung Cancer, and Triple-Negative Breast Cancer.Biomedicines · 2026Article
- Enhancing Specificity, Precision, Accessibility, Flexibility, and Safety to Overcome Traditional CRISPR/Cas Editing Challenges and Shape Future Innovations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Conversion of Ku80 K568 crotonylation to SUMOylation facilitates DNA non-homologous end joining and cancer radioresistance.Signal transduction and targeted therapy · 2025Article
- Genistein Implications in Radiotherapy: Kill Two Birds with One Stone.Molecules (Basel, Switzerland) · 2025Review
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- A perspective on tumor radiation resistance following high-LET radiation treatment.Journal of cancer research and clinical oncology · 2024Review
- DNA-PKcs/AKT1 inhibits epithelial-mesenchymal transition during radiation-induced pulmonary fibrosis by inducing ubiquitination and degradation of Twist1.Clinical and translational medicine · 2024Article
- Review
- Genome-wide analysis of DNA-PK-bound MRN cleavage products supports a sequential model of DSB repair pathway choice.Nature communications · 2023Article
- ATM phosphorylates the FATC domain of DNA-PKcs at threonine 4102 to promote non-homologous end joining.Nucleic acids research · 2023Article
- Heavy metal ions exchange driven protein phosphorylation cascade functions in genomic instability in spermatocytes and male infertility.Nucleic acids research · 2023Article
- TRIM24 is critical for the cellular response to DNA double-strand breaks through regulating the recruitment of MRN complex.Oncogene · 2023Article
- Targeting DNA-PK.Cancer treatment and research · 2023Article
- Partial deletions of the autoregulatory C-terminal domain of Artemis and their effect on its nuclease activity.DNA repair · 2022Article
- Article
- Small Cajal body-associated RNA 2 (scaRNA2) regulates DNA repair pathway choice by inhibiting DNA-PK.Nature communications · 2022Article
- Autophosphorylation transforms DNA-PK from protecting to processing DNA ends.Molecular cell · 2022Article
- Reconsidering pathway choice: a sequential model of mammalian DNA double-strand break pathway decisions.Current opinion in genetics & development · 2021Review
- To Join or Not to Join: Decision Points Along the Pathway to Double-Strand Break Repair vs. Chromosome End Protection.Frontiers in cell and developmental biology · 2021Review
- ATM antagonizes NHEJ proteins assembly and DNA-ends synapsis at single-ended DNA double strand breaks.Nucleic acids research · 2020Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
The resection of DNA double strand breaks initiates homologous recombination (HR) and is critical for genomic stability. Using direct measurement of resection in human cells and reconstituted assays of resection with purified proteins in vitro, we show that DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a classic nonhomologous end joining factor, antagonizes double strand break resection by blocking the recruitment of resection enzymes such as exonuclease 1 (Exo1). Autophosphorylation of DNA-PKcs promotes DNA-PKcs dissociation and consequently Exo1 binding. Ataxia telangiectasia-mutated kinase activity can compensate for DNA-PKcs autophosphorylation and promote resection under conditions where DNA-PKcs catalytic activity is inhibited. The Mre11-Rad50-Nbs1 (MRN) complex further stimulates resection in the presence of Ku and DNA-PKcs by recruiting Exo1 and enhancing DNA-PKcs autophosphorylation, and it also inhibits DNA ligase IV/XRCC4-mediated end rejoining. This work suggests that, in addition to its key role in nonhomologous end joining, DNA-PKcs also acts in concert with MRN and ataxia telangiectasia-mutated to regulate resection and thus DNA repair pathway choice.
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Registered trials
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