ArticleNucleic acids research2023
DNA-PK is activated by SIRT2 deacetylation to promote DNA double-strand break repair by non-homologous end joining.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- MRE11 deacetylation by SIRT2 promotes DNA binding to facilitate DNA end resection and ATM-dependent signaling.The Journal of clinical investigation · 2026Article
- SIRT2 mitigates radiation-induced oral mucositis by promoting homologous recombination-mediated DNA double-strand break repair in epithelial stem cells.Cancer letters · 2026Article
- Chromatin-associated circRNA ciCRLF3(2) regulates cell differentiation blockage via activating non-homologous end joining-based DNA repair.Cell death and differentiation · 2026Article
- Natural Flavonoids Genistein and Baicalein as Well-Tolerated Radiosensitizers to Enhance the Efficacy ofResearch (Washington, D.C.) · 2026Article
- Regulation of drug resistance in bladder urothelial carcinoma by tumor aerobic glycolysis.Journal of translational medicine · 2025Review
- Review
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- PRKDC Induces Chemoresistance in Osteosarcoma by Recruiting GDE2 to Stabilize GNAS and Activate AKT.Cancer research · 2024Article
- Multifaceted regulation of sirtuin 2 (Sirt2) deacetylase activity.The Journal of biological chemistry · 2024Article
- 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
- GCN5 mediates DNA-PKcs crotonylation for DNA double-strand break repair and determining cancer radiosensitivity.British journal of cancer · 2024Article
- New Discoveries on Protein Recruitment and Regulation during the Early Stages of the DNA Damage Response Pathways.International journal of molecular sciences · 2024Review
- Key molecular DNA damage responses of human cells to radiation.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 5 institutions in 1 country.
Funding
Abstract
DNA-dependent protein kinase (DNA-PK) plays a critical role in non-homologous end joining (NHEJ), the predominant pathway that repairs DNA double-strand breaks (DSB) in response to ionizing radiation (IR) to govern genome integrity. The interaction of the catalytic subunit of DNA-PK (DNA-PKcs) with the Ku70/Ku80 heterodimer on DSBs leads to DNA-PK activation; however, it is not known if upstream signaling events govern this activation. Here, we reveal a regulatory step governing DNA-PK activation by SIRT2 deacetylation, which facilitates DNA-PKcs localization to DSBs and interaction with Ku, thereby promoting DSB repair by NHEJ. SIRT2 deacetylase activity governs cellular resistance to DSB-inducing agents and promotes NHEJ. SIRT2 furthermore interacts with and deacetylates DNA-PKcs in response to IR. SIRT2 deacetylase activity facilitates DNA-PKcs interaction with Ku and localization to DSBs and promotes DNA-PK activation and phosphorylation of downstream NHEJ substrates. Moreover, targeting SIRT2 with AGK2, a SIRT2-specific inhibitor, augments the efficacy of IR in cancer cells and tumors. Our findings define a regulatory step for DNA-PK activation by SIRT2-mediated deacetylation, elucidating a critical upstream signaling event initiating the repair of DSBs by NHEJ. Furthermore, our data suggest that SIRT2 inhibition may be a promising rationale-driven therapeutic strategy for increasing the effectiveness of radiation therapy.
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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.