ArticleOncogenesis2021
Loss of p53 suppresses replication stress-induced DNA damage in ATRX-deficient neuroblastoma.
Article in Oncogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- Telomere maintenance mechanisms are activated in ganglioneuroblastoma and ganglioneuroma.Oncology letters · 2026Article
- ATRX loss couples genome instability at a G-rich repeat to dysregulation of human alpha-globin expression.Nature communications · 2026Article
- From Classical to Emerging Biomarkers of Brain and Central Nervous System Tumors. An Evidence-Based Review with a Focus on Gliomas.Cellular and molecular neurobiology · 2026Review
- Pathway for the Development of ATR Inhibitors in Pediatric Malignancies: An ACCELERATE Multistakeholder Analysis.JCO precision oncology · 2026Review
- KCTD10 as a selective cancer dependency from transcription-replication conflicts (TRCs).Ageing and cancer research & treatment · 2026Article
- Alternative Lengthening of Telomeres: The Need forInternational journal of molecular sciences · 2025Article
- Vaccine therapies for glioma: clinical frontiers and potential breakthrough.Frontiers in oncology · 2025Review
- Establishment and characterization of a novel MDM2/MYCN-co-amplified neuroblastoma cell line, NBN-SHIM, established from a late recurrent stage MS tumor.Human cell · 2024Article
- Transplantation of Neural Stem Cells-Overexpressed Ku70 Improves Neurological Deficits in a Mice Model of Cerebral Ischemia Stroke.Neurochemical research · 2024Article
- Effects of p53 and ATRX inhibition on telomeric recombination in aging fibroblasts.Frontiers in oncology · 2024Article
- Inhibition of p53 and ATRX increases telomeric recombination in primary fibroblasts.FEBS open bio · 2023Article
- Conserved G-Quadruplex-Forming Sequences in MammalianLife (Basel, Switzerland) · 2023Article
- ATM depletion induces proteasomal degradation of FANCD2 and sensitizes neuroblastoma cells to PARP inhibitors.BMC cancer · 2023Article
- Connecting telomere maintenance and regulation to the developmental origin and differentiation states of neuroblastoma tumor cells.Journal of hematology & oncology · 2022Review
- Regulation of Replication Stress in Alternative Lengthening of Telomeres by Fanconi Anaemia Protein.Genes · 2022Review
- Tumor Suppressor microRNAs in Gastrointestinal Cancers: A Mini-Review.Recent advances in inflammation & allergy drug discovery · 2022Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Genetic aberrations are present in the ATRX gene in older high-risk neuroblastoma (NB) patients with very poor clinical outcomes. Its loss-of-function (LoF) facilitates the alternative lengthening of telomeres (ALT) pathway in tumor cells and is strongly linked to replication stress (RS) and DNA damage through G-quadruplex (G4) DNA secondary structures. However, limited information is available on ATRX alteration-related NB tumorigenesis. We herein knocked out (KO) ATRX in MYCN-amplified (NGP) and MYCN single copy (SK-N-AS) NB cells with wild-type (wt) and truncated TP53 at the C terminus, respectively, using CRISPR/Cas9 technologies. The loss of ATRX increased DNA damage and G4 formation related to RS in TP53 wt isogenic ATRX KO NGP cells, but not in SK-N-AS clones. A gene set enrichment analysis (GSEA) showed that the gene sets related to DNA double-strand break repair, negative cell cycle regulation, the G2M checkpoint, and p53 pathway activation were enriched in NGP clones. The accumulation of DNA damage activated the ATM/CHK2/p53 pathway, leading to cell cycle arrest in NGP clones. Interestingly, ATRX loss did not induce RS related to DNA damage response (DDR) in TP53-truncated SK-N-AS cells. p53 inactivation abrogated cell cycle arrest and reduced G4 accumulation in NGP clones. The loss of p53 also induced G4 DNA helicases or Fanconi anemia group D2 protein (FANCD2) with ATRX deficiency, suggesting that ATRX maintained genome integrity and p53 deficiency attenuated RS-induced DNA damage in NB cells featuring inactivated ATRX by regulating DNA repair mechanisms and replication fork stability.
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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.