ArticleProceedings of the National Academy of Sciences of the United States of America2018
Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 99 citations in OpenAlex.
- The ATRXt Protein Represses rDNA Transcription While Mirroring ATRX Interactions and Heterochromatin Localization.International journal of molecular sciences · 2026Article
- The EHMT2-MBLAC2 axis suppresses ribosomal DNA transcription in response to nucleolar DNA damage.Cell death & disease · 2026Article
- A Double-Edged Role for SIRT7 in Cancer: Can Anti-Cancer Immunity Tip the Balance?Pharmaceuticals (Basel, Switzerland) · 2025Review
- C8orf33 dictates DNA double-strand break repair choice by modulating KAT8-mediated H4K16 acetylation.Cell death & disease · 2025Article
- Phenotypic tolerance for rDNA copy number variation within the natural range of C. elegans.PLoS genetics · 2025Article
- The G-quadruplex ligand CX-5461: an innovative candidate for disease treatment.Journal of translational medicine · 2025Review
- Assessing Human Ribosomal DNA Variation and Its Association With Phenotypic Outcomes.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- It Takes a Village of Chromatin Remodelers to Regulate rDNA Expression.International journal of molecular sciences · 2025Review
- Simultaneous quantification of rDNA methylation and copy number: Constraints to natural variation in humans and cell lines.PloS one · 2025Article
- A First-in-Class High-Throughput Screen to Discover Modulators of the Alternative Lengthening of Telomeres (ALT) Pathway.ACS pharmacology & translational science · 2024Article
- Diversity of ribosomes at the level of rRNA variation associated with human health and disease.Cell genomics · 2024Article
- Ribosomal DNA copy number is associated with body mass in humans and other mammals.Nature communications · 2024Article
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- Mutant ATRX: pathogenesis of ATRX syndrome and cancer.Frontiers in molecular biosciences · 2024Review
- Pediatric glioma histone H3.3 K27M/G34R mutations drive abnormalities in PML nuclear bodies.Genome biology · 2023Article
- Substantial rDNA copy number reductions alter timing of development and produce variable tissue-specific phenotypes in C. elegans.Genetics · 2023Article
- Targeting RNA Polymerase I Transcription Activity in Osteosarcoma: Pre-Clinical Molecular and Animal Treatment Studies.Biomedicines · 2023Article
- ATRX loss suppresses the type I interferon response in sarcoma cells through chromatin remodeling.American journal of cancer research · 2023Article
- Article
- Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors. Further investigation shows that the rDNA copy loss and repeat instability are caused by a disruption in H3.3 deposition and thus a failure in heterochromatin formation at rDNA repeats in the absence of ATRX. We also find that ATRX-depleted cells are reduced in ribosomal RNA transcription output and show increased sensitivity to RNA polymerase I (Pol I) transcription inhibitor CX5461. In addition, human ALT-positive cancer cell lines are also more sensitive to CX5461 treatment. Our study provides insights into the contribution of ATRX loss of function to tumorigenesis through the loss of rDNA stability and suggests the therapeutic potential of targeting Pol I transcription in ALT cancers.
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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.