ArticleNucleic acids research2019
Double-strand breaks in ribosomal RNA genes activate a distinct signaling and chromatin response to facilitate nucleolar restructuring and repair.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 102 citations in OpenAlex.
- Nucleolar reorganization on stress depends on physicochemical changes due to reduced nascent rRNA synthesis.EMBO reports · 2026Article
- Peroxiredoxin 1 safeguards the nucleolar genome from oxidative damage.Science advances · 2026Article
- RAD54L coordinates the nucleolar DNA damage response to maintain rDNA stability.The EMBO journal · 2026Article
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- TCOF1 in extracellular vesicles predicts survival in patients with HCC treated with high-dose conformal radiotherapy.JHEP reports : innovation in hepatology · 2026Article
- The histone methyltransferase NSD3 oncogene triggers ribosomal DNA transcription, interfering with FOSL2 in cancer.Cell death & disease · 2026Article
- The EHMT2-MBLAC2 axis suppresses ribosomal DNA transcription in response to nucleolar DNA damage.Cell death & disease · 2026Article
- Ribosome biogenesis is increased in hepatocellular carcinoma and represents a potential therapeutic target.NAR cancer · 2026Article
- Visualization and quantification of rDNA instabilities in mammalian cells and mouse models.Nucleic acids research · 2026Article
- Nucleolus as a cornerstone linking proliferation and metabolism to cellular responses to stress: involvement of transcription factors MYC and p53.Frontiers in molecular biosciences · 2026Review
- C8orf33 dictates DNA double-strand break repair choice by modulating KAT8-mediated H4K16 acetylation.Cell death & disease · 2025Article
- Peroxiredoxin 1 safeguards the nucleolar genome from oxidative damage.bioRxiv : the preprint server for biology · 2025Article
- Nucleolar Organization in Response to Transcriptional Stress.Cancer science · 2025Review
- A High-Throughput ImmunoHistoFluorescence (IHF) Method for Sub-Nuclear Protein Analysis in Tissue.Cells · 2025Article
- Nuclear and genome dynamics underlying DNA double-strand break repair.Nature reviews. Molecular cell biology · 2025Review
- HIV Vpr activates a nucleolar-specific ATR pathway to degrade the nucleolar stress sensor CCDC137.Nucleic acids research · 2025Article
- Article
- Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma.Science advances · 2025Article
- NBS1 facilitates preribosomal RNA biogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Identification of Fanconi anemia pathway genes as novel prognostic biomarkers and therapeutic targets for breast cancer.Translational cancer research · 2025Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nucleolus is a nuclear sub-domain containing the most highly transcribed genes in the genome. Hundreds of human ribosomal RNA (rRNA) genes, located in the nucleolus, rely on constant maintenance. DNA double-strand breaks (DSBs) in rRNA genes activate the ATM kinase, repress rRNA transcription and induce nucleolar cap formation. Yet how ribosomal-DNA (rDNA) lesions are detected and processed remains elusive. Here, we use CRISPR/Cas9-mediated induction of DSBs and report a chromatin response unique to rDNA depending on ATM-phosphorylation of the nucleolar protein TCOF1 and recruitment of the MRE11-RAD50-NBS1 (MRN) complex via the NBS1-subunit. NBS1- and MRE11-depleted cells fail to suppress rRNA transcription and to translocate rDNA into nucleolar caps. Furthermore, the DNA damage response (DDR) kinase ATR operates downstream of the ATM-TCOF1-MRN interplay and is required to fully suppress rRNA transcription and complete DSB-induced nucleolar restructuring. Unexpectedly, we find that DSBs in rDNA neither activate checkpoint kinases CHK1/CHK2 nor halt cell-cycle progression, yet the nucleolar-DDR protects against genomic aberrations and cell death. Our data highlight the concept of a specialized nucleolar DNA damage response (n-DDR) with a distinct protein composition, spatial organization and checkpoint communication. The n-DDR maintains integrity of ribosomal RNA genes, with implications for cell physiology and disease.
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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.