ArticleThe EMBO journal2020
Nucleotide depletion reveals the impaired ribosome biogenesis checkpoint as a barrier against DNA damage.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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
26 citing papers in PubMed, 36 citations in OpenAlex.
- JP-1302 inhibits RNA polymerase I transcription and induces nucleolar stress in cancer cell lines.Cell death discovery · 2026Article
- Transcriptional Profiling at Single-Cell Resolution Reveals Diversity and Regulatory Networks of Primary and Secondary Senescent Cells.Aging cell · 2026Article
- Article
- Loss of UXS1 Selectively Depletes Pyrimidines and Induces Replication Stress in KEAP1-Mutant Lung Cancer.Cancer research · 2025Article
- Human iPSC-derived salivary gland organoids model diabetic salivary gland dysfunction.bioRxiv : the preprint server for biology · 2025Article
- SNORD113-114 cluster maintains haematopoietic stem cell self-renewal via orchestrating the translation machinery.Nature cell biology · 2025Article
- Coordination between the eIF2 kinase GCN2 and p53 signaling supports purine metabolism and the progression of prostate cancer.Science signaling · 2024Article
- Nuclear IMPDH2 controls the DNA damage response by modulating PARP1 activity.Nature communications · 2024Article
- SURF2 is a MDM2 antagonist in triggering the nucleolar stress response.Nature communications · 2024Article
- Rational design of an artificial tethered enzyme for non-templated post-transcriptional mRNA polyadenylation by the second generation of the C3P3 system.Scientific reports · 2024Article
- Ribosomal protein mutations and cell competition: autonomous and nonautonomous effects on a stress response.Genetics · 2023Article
- Mitochondrial complex III deficiency drives c-MYC overexpression and illicit cell cycle entry leading to senescence and segmental progeria.Nature communications · 2023Article
- Potential prognostic and predictive value of UBE2N, IMPDH1, DYNC1LI1 and HRASLS2 in colorectal cancer stool specimens.Biomedical reports · 2023Article
- Ribosome biogenesis in disease: new players and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Ribosome-Directed Therapies in Cancer.Biomedicines · 2022Review
- Nucleotide imbalance decouples cell growth from cell proliferation.Nature cell biology · 2022Article
- The consequences of viral infection on host DNA damage response: a focus on SARS-CoVs.Journal, genetic engineering & biotechnology · 2022Review
- p53 at the crossroad of DNA replication and ribosome biogenesis stress pathways.Cell death and differentiation · 2022Review
- Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy.Journal of hematology & oncology · 2022Review
- Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
Many oncogenes enhance nucleotide usage to increase ribosome content, DNA replication, and cell proliferation, but in parallel trigger p53 activation. Both the impaired ribosome biogenesis checkpoint (IRBC) and the DNA damage response (DDR) have been implicated in p53 activation following nucleotide depletion. However, it is difficult to reconcile the two checkpoints operating together, as the IRBC induces p21-mediated G1 arrest, whereas the DDR requires that cells enter S phase. Gradual inhibition of inosine monophosphate dehydrogenase (IMPDH), an enzyme required for de novo GMP synthesis, reveals a hierarchical organization of these two checkpoints. We find that the IRBC is the primary nucleotide sensor, but increased IMPDH inhibition leads to p21 degradation, compromising IRBC-mediated G1 arrest and allowing S phase entry and DDR activation. Disruption of the IRBC alone is sufficient to elicit the DDR, which is strongly enhanced by IMPDH inhibition, suggesting that the IRBC acts as a barrier against genomic instability.
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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.