ArticleThe EMBO journal2012
Endogenous DNA replication stress results in expansion of dNTP pools and a mutator phenotype.
Article in The EMBO journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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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.
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Who cites it
68 citing papers in PubMed, 104 citations in OpenAlex.
- Altered dNTP pools accelerate tumor formation in mice.Nucleic acids research · 2024Article
- Understanding the interplay between dNTP metabolism and genome stability in cancer.Disease models & mechanisms · 2024Review
- S-phase checkpoint prevents leading strand degradation from strand-associated nicks at stalled replication forks.Nucleic acids research · 2024Article
- Profiling the compendium of changes in Saccharomyces cerevisiae due to mutations that alter availability of the main methyl donor S-Adenosylmethionine.G3 (Bethesda, Md.) · 2024Article
- Article
- TYMS promotes genomic instability and tumor progression in Ink4a/Arf null background.Oncogene · 2023Article
- A nuclear orthologue of the dNTP triphosphohydrolase SAMHD1 controls dNTP homeostasis and genomic stability inFrontiers in cellular and infection microbiology · 2023Article
- Persistent Acetylation of Histone H3 Lysine 56 Compromises the Activity of DNA Replication Origins.Molecular and cellular biology · 2023Article
- Article
- Peroxiredoxin, Senescence, and Cancer.Cells · 2022Review
- Chl1 helicase controls replication fork progression by regulating dNTP pools.Life science alliance · 2022Article
- dNTPpoolDB: a manually curated database of experimentally determined dNTP pools and pool changes in biological samples.Nucleic acids research · 2022Article
- Cosegregation of asymmetric features during cell division.Open biology · 2021Article
- Frataxin deficiency promotes endothelial senescence in pulmonary hypertension.The Journal of clinical investigation · 2021Article
- Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.American journal of human genetics · 2020Article
- Quantitation of deoxynucleoside triphosphates by click reactions.Scientific reports · 2020Article
- Article
- Dysfunctional CAF-I reveals its role in cell cycle progression and differential regulation of gene silencing.Cell cycle (Georgetown, Tex.) · 2019Article
- Mutations in the S-Adenosylmethionine Synthetase GenesGenetics · 2019Article
- Mck1 defines a key S-phase checkpoint effector in response to various degrees of replication threats.PLoS genetics · 2019Article
8 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
13 authors at 5 institutions in 4 countries.
Funding
Abstract
The integrity of the genome depends on diverse pathways that regulate DNA metabolism. Defects in these pathways result in genome instability, a hallmark of cancer. Deletion of ELG1 in budding yeast, when combined with hypomorphic alleles of PCNA results in spontaneous DNA damage during S phase that elicits upregulation of ribonucleotide reductase (RNR) activity. Increased RNR activity leads to a dramatic expansion of deoxyribonucleotide (dNTP) pools in G1 that allows cells to synthesize significant fractions of the genome in the presence of hydroxyurea in the subsequent S phase. Consistent with the recognized correlation between dNTP levels and spontaneous mutation, compromising ELG1 and PCNA results in a significant increase in mutation rates. Deletion of distinct genome stability genes RAD54, RAD55, and TSA1 also results in increased dNTP levels and mutagenesis, suggesting that this is a general phenomenon. Together, our data point to a vicious circle in which mutations in gatekeeper genes give rise to genomic instability during S phase, inducing expansion of the dNTP pool, which in turn results in high levels of spontaneous mutagenesis.
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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.