ArticleProceedings of the National Academy of Sciences of the United States of America2011
Increase in dNTP pool size during the DNA damage response plays a key role in spontaneous and induced-mutagenesis in Escherichia coli.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 106 citations in OpenAlex.
- Article
- Review
- Continuous assay for the dNTP triphosphohydrolase of activated SAMHD1.Analytical biochemistry · 2026Article
- Antimutator and Mutational Spectrum Effects Can Combine to Reduce Evolutionary Potential in Escherichia coli ΔnudJ.Molecular biology and evolution · 2025Article
- An additional replication origin causes cell cycle specific DNA replication fork speed.Frontiers in microbiology · 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
- Understanding the interplay between dNTP metabolism and genome stability in cancer.Disease models & mechanisms · 2024Review
- SOS genes are rapidly induced while translesion synthesis polymerase activity is temporally regulated.Frontiers in microbiology · 2024Article
- A nuclear orthologue of the dNTP triphosphohydrolase SAMHD1 controls dNTP homeostasis and genomic stability inFrontiers in cellular and infection microbiology · 2023Article
- Enhanced polymerase activity permits efficient synthesis by cancer-associated DNA polymerase ϵ variants at low dNTP levels.Nucleic acids research · 2022Article
- Single strand gap repair: The presynaptic phase plays a pivotal role in modulating lesion tolerance pathways.PLoS genetics · 2022Article
- Improved dsDNA recombineering enables versatile multiplex genome engineering of kilobase-scale sequences in diverse bacteria.Nucleic acids research · 2022Article
- Still no Rest for the Reductases: Ribonucleotide Reductase (RNR) Structure and Function: An Update.Sub-cellular biochemistry · 2022Review
- Elevated Levels of the Escherichia coliJournal of bacteriology · 2021Article
- Article
- Enhanced nucleotide analysis enables the quantification of deoxynucleotides in plants and algae revealing connections between nucleoside and deoxynucleoside metabolism.The Plant cell · 2021Article
- Protective Effect of Thymidine on DNA Damage Induced by Hydrogen Peroxide in Human Hepatocellular Cancer Cells.ACS omega · 2020Article
- Diverse roles of nucleoside diphosphate kinase in genome stability and growth fitness.Current genetics · 2020Review
- Bacterial phenotypic heterogeneity in DNA repair and mutagenesis.Biochemical Society transactions · 2020Review
17 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exposure of Escherichia coli to UV light increases expression of NrdAB, the major ribonucleotide reductase leading to a moderate increase in dNTP levels. The role of elevated dNTP levels during translesion synthesis (TLS) across specific replication-blocking lesions was investigated. Here we show that although the specialized DNA polymerase PolV is necessary for replication across UV-lesions, such as cyclobutane pyrimidine dimers or pyrimidine(6-4)pyrimidone photoproduct, Pol V per se is not sufficient. Indeed, efficient TLS additionally requires elevated dNTP levels. Similarly, for the bypass of an N-2-acetylaminofluorene-guanine adduct that requires Pol II instead of PolV, efficient TLS is only observed under conditions of high dNTP levels. We suggest that increased dNTP levels transiently modify the activity balance of Pol III (i.e., increasing the polymerase and reducing the proofreading functions). Indeed, we show that the stimulation of TLS by elevated dNTP levels can be mimicked by genetic inactivation of the proofreading function (mutD5 allele). We also show that spontaneous mutagenesis increases proportionally to dNTP pool levels, thus defining a unique spontaneous mutator phenotype. The so-called "dNTP mutator" phenotype does not depend upon any of the specialized DNA polymerases, and is thus likely to reflect an increase in Pol III's own replication errors because of the modified activity balance of Pol III. As up-regulation of the dNTP pool size represents a common physiological response to DNA damage, the present model is likely to represent a general and unique paradigm for TLS pathways in many organisms.
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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.