ArticleNature cell biology2022
Nucleotide imbalance decouples cell growth from cell proliferation.
Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
116 citing papers in PubMed, 198 citations in OpenAlex.
- Ribonucleotides Amplify Mitochondrial DNA-Driven cGAS-STING Activation via FdUMP-ribonucleotide Hybrid Particles to Potentiate Chemoimmunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Physiological folate levels constrain nucleotide synthesis and increase dependence on nucleotide salvage.bioRxiv : the preprint server for biology · 2026Article
- Loss of BOK increases vulnerability of p53 deficient non-small cell lung cancer cells to ATR inhibition through its role in uridine metabolism.Cell death and differentiation · 2026Article
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- Metabolic alterations in Snyder-Robinson syndrome lymphoblasts are ameliorated by phenylbutyrate treatment.Molecular genetics and metabolism · 2026Article
- Metabolic adaptations of starving purple sea urchins (Strongylocentrotus purpuratus) surviving in the barrens.Scientific reports · 2026Article
- Histone H3.3 ensures cell proliferation and genomic stability during myeloid cell development.iScience · 2026Article
- Arginine metabolism supportsmBio · 2026Article
- Nuclear adenosine metabolism defines a metabolic vulnerability unmasked by TP53 loss.bioRxiv : the preprint server for biology · 2026Article
- ATF4 coordinates amino acid and nucleotide synthesis with selective protein translation to ensure proper DNA replication timing in leukemia cells.Nature communications · 2026Article
- Beyond Urease: New Potential Enzymatic Targets inACS omega · 2026Review
- Network Clustering Approach Reveals Key Proteins and Biological Functions in the Response of Whiteleg Shrimp (Penaeus vannamei) to Acute Hepatopancreatic Necrosis Disease.Marine biotechnology (New York, N.Y.) · 2026Article
- Metab8D: a metabolic regulome network from multiomics and machine learning.Communications biology · 2026Article
- Enhancer and metabolic rewiring by KMT2C-COMPASS or KMT2D-COMPASS family loss in cancer creates druggable vulnerabilities.Nature reviews. Cancer · 2026Review
- Cell Cycle Control of Nuclear Metabolism Couples Phosphatidylinositol Signaling to Histone Methylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase.Nature metabolism · 2026Article
- Unraveling the Taxonomic Diversity and Functional Potential of the Tunisian Salterns, Abbassia and Thyna, via Integrated 16S-18S Amplicons and Shotgun Metagenomics.International journal of molecular sciences · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- OGDHL Promotes Prostate Cancer Progression and Regulates Neuroendocrine Marker Expression and Nucleotide Abundance.Molecular cancer research : MCR · 2026Article
- Oncogenic DCTPP1/MYC feedback loop rewires pyrimidine metabolism to drive hepatocellular carcinoma.Functional & integrative genomics · 2026Article
56 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
9 authors at 6 institutions in 2 countries.
Funding
Abstract
Nucleotide metabolism supports RNA synthesis and DNA replication to enable cell growth and division. Nucleotide depletion can inhibit cell growth and proliferation, but how cells sense and respond to changes in the relative levels of individual nucleotides is unclear. Moreover, the nucleotide requirement for biomass production changes over the course of the cell cycle, and how cells coordinate differential nucleotide demands with cell cycle progression is not well understood. Here we find that excess levels of individual nucleotides can inhibit proliferation by disrupting the relative levels of nucleotide bases needed for DNA replication and impeding DNA replication. The resulting purine and pyrimidine imbalances are not sensed by canonical growth regulatory pathways like mTORC1, Akt and AMPK signalling cascades, causing excessive cell growth despite inhibited proliferation. Instead, cells rely on replication stress signalling to survive during, and recover from, nucleotide imbalance during S phase. We find that ATR-dependent replication stress signalling is activated during unperturbed S phases and promotes nucleotide availability to support DNA replication. Together, these data reveal that imbalanced nucleotide levels are not detected until S phase, rendering cells reliant on replication stress signalling to cope with this metabolic problem and disrupting the coordination of cell growth and division.
Indexed as
Identifiers
What OpenQuestion holds
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.