ArticleNucleic acids research2010
Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpoint.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed.
- Structure-guided engineering of human thymidine kinase 2 as a positron emission tomography reporter gene for enhanced phosphorylation of non-natural thymidine analog reporter probe.The Journal of biological chemistry · 2012Trial
- Physiological folate levels constrain nucleotide synthesis and increase dependence on nucleotide salvage.bioRxiv : the preprint server for biology · 2026Article
- Hypermutability ofEmerging microbes & infections · 2025Article
- Functionally dominant hotspot mutations of mitochondrial ribosomal RNA genes in cancer.Nature genetics · 2025Article
- CYB5R4 sustains endothelial proliferation and ischemia-induced angiogenesis by maintaining RRM2-dependent nucleotide balance.bioRxiv : the preprint server for biology · 2025Article
- SHMT2 is essential for mammalian preimplantation embryonic development throughMolecular therapy. Nucleic acids · 2025Article
- RNA-DNA Differences: Mechanisms, Oxidative Stress, Transcriptional Fidelity, and Health Implications.Antioxidants (Basel, Switzerland) · 2025Review
- Vulnerable Nucleotide Pools and Genomic Instability in Yeast Strains with Deletion of theInternational journal of molecular sciences · 2025Article
- Clues to transcription/replication collision-induced DNA damage: it was RNAP, in the chromosome, with the fork.FEBS letters · 2025Review
- Genetic stability ofeLife · 2024Article
- Altered dNTP pools accelerate tumor formation in mice.Nucleic acids research · 2024Article
- Altered S-AdenosylMethionine availability impacts dNTP pools in Saccharomyces cerevisiae.Yeast (Chichester, England) · 2024Article
- Metabolic clogging of mannose triggers dNTP loss and genomic instability in human cancer cells.eLife · 2023Article
- From a drug repositioning to a structure-based drug design approach to tackle acute lymphoblastic leukemia.Nature communications · 2023Article
- A nuclear orthologue of the dNTP triphosphohydrolase SAMHD1 controls dNTP homeostasis and genomic stability inFrontiers in cellular and infection microbiology · 2023Article
- dTMP imbalance through thymidylate 5'-phosphohydrolase activity induces apoptosis in triple-negative breast cancers.Scientific reports · 2022Article
- DNA replication timing: Biochemical mechanisms and biological significance.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Nucleotide imbalance decouples cell growth from cell proliferation.Nature cell biology · 2022Article
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37 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A balanced supply of deoxyribonucleoside triphosphates (dNTPs) is one of the key prerequisites for faithful genome duplication. Both the overall concentration and the balance among the individual dNTPs (dATP, dTTP, dGTP, and dCTP) are tightly regulated, primarily by the enzyme ribonucleotide reductase (RNR). We asked whether dNTP pool imbalances interfere with cell cycle progression and are detected by the S-phase checkpoint, a genome surveillance mechanism activated in response to DNA damage or replication blocks. By introducing single amino acid substitutions in loop 2 of the allosteric specificity site of Saccharomyces cerevisiae RNR, we obtained a collection of strains with various dNTP pool imbalances. Even mild dNTP pool imbalances were mutagenic, but the mutagenic potential of different dNTP pool imbalances did not directly correlate with their severity. The S-phase checkpoint was activated by the depletion of one or several dNTPs. In contrast, when none of the dNTPs was limiting for DNA replication, even extreme and mutagenic dNTP pool imbalances did not activate the S-phase checkpoint and did not interfere with the cell cycle progression.
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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.