ArticleScience advances2023
SMYD2 inhibition-mediated hypomethylation of Ku70 contributes to impaired nonhomologous end joining repair and antitumor immunity.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 26 citations in OpenAlex.
- Unmasking Wnt-driven HCC: Inhibiting SMYD2 to overcome immune resistance.Molecular therapy. Oncology · 2026Article
- Insights into Ovarian Cancer: Unraveling the Role of DNA Double-strand Break-related Genes in Pathogenesis and Therapeutic Avenues.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Targeting SMYD2 improves immunotherapy response in experimental hepatocellular carcinoma.Molecular therapy. Oncology · 2026Article
- mCell death and differentiation · 2026Article
- FOXN3 integrates the KU70/KU80/SREBP-1 complex to regulate lipid metabolism in non-alcoholic fatty liver disease.Nucleic acids research · 2026Article
- Nanomedicine leverages cuproptosis-mediated cGAS-STING activation to enhance antitumor immunity.Journal of nanobiotechnology · 2026Review
- Chromatin-associated circRNA ciCRLF3(2) regulates cell differentiation blockage via activating non-homologous end joining-based DNA repair.Cell death and differentiation · 2026Article
- Inhibiting macrophage-derived lactate transport restores cGAS-STING signalling and enhances antitumour immunity in glioblastoma.Nature cell biology · 2026Article
- ZAK kinase at the crossroads of cellular stress: functional plasticity, human pathobiology, and precision therapeutics.Frontiers in cell and developmental biology · 2026Review
- cGAS-STING and PANoptosis: Interplay, Underlying Mechanisms, and Therapeutic Targets.Drug design, development and therapy · 2026Review
- ACOX2 destabilizes the MRE11-RAD50-NBS1 complex and boosts anticancer immunity via the cGAS-STING pathway in clear cell renal cell carcinoma.Molecular cancer · 2025Article
- Targeting the interplay of cGAS-STING and ferroptosis by nanomedicine in the treatment of cancer.Journal of experimental & clinical cancer research : CR · 2025Review
- Role of SMYD2 in gastrointestinal cancer progression (Review).Oncology letters · 2025Review
- SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner.Nature communications · 2025Article
- Homeodomain protein PRRX1 anchors the Ku heterodimers at DNA double-strand breaks to promote nonhomologous end-joining.Nucleic acids research · 2025Article
- Identification of SMYD2 as a candidate diagnostic and prognostic biomarker for gastric cancer.Frontiers in oncology · 2025Article
- GLTSCR1 deficiency promotes colorectal cancer development through regulating non-homologous end joining.Oncogene · 2024Article
- DOT1L-mediated RAP80 methylation promotes BRCA1 recruitment to elicit DNA repair.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Lysine methylation modifications in tumor immunomodulation and immunotherapy: regulatory mechanisms and perspectives.Biomarker research · 2024Review
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA damage repair (DDR) is a double-edged sword with different roles in cancer susceptibility and drug resistance. Recent studies suggest that DDR inhibitors affect immune surveillance. However, this phenomenon is poorly understood. We report that methyltransferase SMYD2 plays an essential role in nonhomologous end joining repair (NHEJ), driving tumor cells adaptive to radiotherapy. Mechanically, in response to DNA damage, SMYD2 is mobilized onto chromatin and methylates Ku70 at lysine-74, lysine-516, and lysine-539, leading to increased recruitment of Ku70/Ku80/DNA-PKcs complex. Knockdown of SMYD2 or its inhibitor AZ505 results in persistent DNA damage and improper repair, which sequentially leads to accumulation of cytosolic DNA, and activation of cGAS-STING pathway and triggers antitumor immunity via infiltration and activation of cytotoxic CD8
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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.