ArticlePLoS genetics2017
DNA replication stress restricts ribosomal DNA copy number.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 107 citations in OpenAlex.
- Narrative review-the emerging role, functions, and mechanisms of UFMylation in cancers.Translational cancer research · 2026Review
- Visualization and quantification of rDNA instabilities in mammalian cells and mouse models.Nucleic acids research · 2026Article
- Identification of Fibrillarin and Cajal Bodies Under DNA Replication Stress Conditions in Root Meristem Cells ofInternational journal of molecular sciences · 2025Article
- Compensatory evolution to DNA replication stress is robust to nutrient availability.Molecular systems biology · 2025Article
- rDNA copy number variation affects yeast fitness in response to different environments.Genetics · 2025Article
- Loss of G1-phase CDK-inhibition biases instability between genomic regions by unevenly reducing activity among replication origins.iScience · 2025Article
- Biomolecular condensates in immune cell fate.Nature reviews. Immunology · 2025Review
- Assessing Human Ribosomal DNA Variation and Its Association With Phenotypic Outcomes.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Article
- Insulin signaling regulates R2 retrotransposon expression to orchestrate transgenerational rDNA copy number maintenance.Nature communications · 2025Article
- Decoding the molecular script of 2'-O-ribomethylation: Implications across CNS disorders.Heliyon · 2024Review
- Sir2 and Fun30 regulate ribosomal DNA replication timing via MCM helicase positioning and nucleosome occupancy.bioRxiv : the preprint server for biology · 2024Article
- Regulators of rDNA array morphology in fission yeast.PLoS genetics · 2024Article
- Directional selection, not the direction of selection, affects telomere length and copy number at ribosomal RNA loci.Scientific reports · 2024Article
- The copy number of the eukaryotic rRNA gene can be counted comprehensively.MicrobiologyOpen · 2024Article
- SIRT1 Prevents R-Loops during Chronological Aging by Modulating DNA Replication at rDNA Loci.Cells · 2023Article
- Contribution of Spontaneous Mutations to Quantitative and Molecular Variation at the Highly Repetitive rDNA Locus in Yeast.Genome biology and evolution · 2023Article
- Ribosomal Intergenic Spacers Are Filled with Transposon Remnants.Genome biology and evolution · 2023Article
- Substantial rDNA copy number reductions alter timing of development and produce variable tissue-specific phenotypes in C. elegans.Genetics · 2023Article
- Ribosomal DNA replication time coordinates completion of genome replication and anaphase in yeast.Cell reports · 2023Article
6 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
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a "normal" rDNA copy number.
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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.