ArticleNucleic acids research2015
High levels of TopBP1 induce ATR-dependent shut-down of rRNA transcription and nucleolar segregation.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- DUSP12 Regulates NAT10-Mediated RNA Acetylation to Modulate DNA Repair and Therapeutic Response in Hepatocellular Carcinoma.MedComm · 2026Article
- NBS1 facilitates preribosomal RNA biogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- HROB Is Implicated in DNA Replication.Genes · 2024Article
- Review
- Article
- Transcriptional inhibition after irradiation occurs preferentially at highly expressed genes in a manner dependent on cell cycle progression.bioRxiv : the preprint server for biology · 2024Article
- Pre-rRNA Facilitates TopBP1-Mediated DNA Double-Strand Break Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Molecular mechanisms of nucleolar DNA damage checkpoint response.Trends in cell biology · 2023Article
- APE1 assembles biomolecular condensates to promote the ATR-Chk1 DNA damage response in nucleolus.Nucleic acids research · 2022Article
- Rad17 Translocates to Nucleolus upon UV Irradiation through Nucleolar Localization Signal in the Central Basic Domain.International journal of molecular sciences · 2022Article
- The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis.Nature communications · 2022Article
- p53 at the crossroad of DNA replication and ribosome biogenesis stress pathways.Cell death and differentiation · 2022Review
- Treacle Sticks the Nucleolar Responses to DNA Damage Together.Frontiers in cell and developmental biology · 2022Review
- Replication protein A associates with nucleolar R loops and regulates rRNA transcription and nucleolar morphology.Genes & development · 2021Article
- Treacle and TOPBP1 control replication stress response in the nucleolus.The Journal of cell biology · 2021Article
- RBMX is required for activation of ATR on repetitive DNAs to maintain genome stability.Cell death and differentiation · 2020Article
- Recent advances in the nucleolar responses to DNA double-strand breaks.Nucleic acids research · 2020Review
- Oxaliplatin-Induced DHX9 Phosphorylation Promotes Oncogenic Circular RNA CCDC66 Expression and Development of Chemoresistance.Cancers · 2020Article
- Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation.Nature communications · 2020Article
- Local inhibition of rRNA transcription without nucleolar segregation after targeted ion irradiation of the nucleolus.Journal of cell science · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleoli are not only organelles that produce ribosomal subunits. They are also overarching sensors of different stress conditions and they control specific nucleolar stress pathways leading to stabilization of p53. During DNA replication, ATR and its activator TopBP1 initiate DNA damage response upon DNA damage and replication stress. We found that a basal level of TopBP1 protein associates with ribosomal DNA repeat. When upregulated, TopBP1 concentrates at the ribosomal chromatin and initiates segregation of nucleolar components--the hallmark of nucleolar stress response. TopBP1-induced nucleolar segregation is coupled to shut-down of ribosomal RNA transcription in an ATR-dependent manner. Nucleolar segregation induced by TopBP1 leads to a moderate elevation of p53 protein levels and to localization of activated p53 to nucleolar caps containing TopBP1, UBF and RNA polymerase I. Our findings demonstrate that TopBP1 and ATR are able to inhibit the synthesis of rRNA and to activate nucleolar stress pathway; yet the p53-mediated cell cycle arrest is thwarted in cells expressing high levels of TopBP1. We suggest that inhibition of rRNA transcription by different stress regulators is a general mechanism for cells to initiate nucleolar stress pathway.
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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.