ArticleNucleic acids research2016
Genome-wide analysis of the specificity and mechanisms of replication infidelity driven by imbalanced dNTP pools.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Two distinct Okazaki fragment failure modes dominate mutagenesis in the absence of flap endonuclease 1.Nature communications · 2026Article
- AVITI sequencing of a four-generation CEPH/Utah pedigree confirms low mutation rates at homopolymer loci despite their low sequence complexity.Genome biology · 2026Article
- The A, B, C, D's of replicative DNA polymerase fidelity: utilizing high-throughput single-molecule sequencing to understand the molecular basis for DNA polymerase accuracy.Nucleic acids research · 2025Article
- AVITI sequencing of a four-generation CEPH/Utah pedigree confirms low mutation rates at homopolymer loci despite their low sequence complexity.bioRxiv : the preprint server for biology · 2025Article
- Evidence that transient replication errors initiate nuclear genome mutations.Nucleic acids research · 2025Article
- A deoxynucleoside triphosphate triphosphohydrolase promotes cell cycle progression inJournal of bacteriology · 2025Article
- Altered S-AdenosylMethionine availability impacts dNTP pools in Saccharomyces cerevisiae.Yeast (Chichester, England) · 2024Article
- Understanding the interplay between dNTP metabolism and genome stability in cancer.Disease models & mechanisms · 2024Review
- Engineering of the DNA replication and repair machinery to develop binary mutators for rapid genome evolution of Corynebacterium glutamicum.Nucleic acids research · 2023Article
- Mutation bias and the predictability of evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Quantitative Analysis of Nucleoside Triphosphate Pools in Mouse Muscle Using Hydrophilic Interaction Liquid Chromatography Coupled with Tandem Mass Spectrometry Detection.Methods in molecular biology (Clifton, N.J.) · 2023Article
- A nuclear orthologue of the dNTP triphosphohydrolase SAMHD1 controls dNTP homeostasis and genomic stability inFrontiers in cellular and infection microbiology · 2023Article
- Essential Roles of Ribonucleotide Reductases under DNA Damage and Replication Stresses in Cryptococcus neoformans.Microbiology spectrum · 2022Article
- Article
- Ribonucleotide Incorporation by Eukaryotic B-Family Replicases and Its Implications for Genome Stability.Annual review of biochemistry · 2022Review
- Breaking the paradigm: early insights from mammalian DNA breakomes.The FEBS journal · 2022Review
- Chl1 helicase controls replication fork progression by regulating dNTP pools.Life science alliance · 2022Article
- Characterization of Photorhabdus Virulence Cassette as a causative agent in the emerging pathogen Photorhabdus asymbiotica.Science China. Life sciences · 2022Article
- dNTPpoolDB: a manually curated database of experimentally determined dNTP pools and pool changes in biological samples.Nucleic acids research · 2022Article
- Article
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Authors and funding
5 authors.
Funding
Abstract
The absolute and relative concentrations of the four dNTPs are key determinants of DNA replication fidelity, yet the consequences of altered dNTP pools on replication fidelity have not previously been investigated on a genome-wide scale. Here, we use deep sequencing to determine the types, rates and locations of uncorrected replication errors that accumulate in the nuclear genome of a mismatch repair-deficient diploid yeast strain with elevated dCTP and dTTP concentrations. These imbalanced dNTP pools promote replication errors in specific DNA sequence motifs suggesting increased misinsertion and increased mismatch extension at the expense of proofreading. Interestingly, substitution rates are similar for leading and lagging strand replication, but are higher in regions replicated late in S phase. Remarkably, the rate of single base deletions is preferentially increased in coding sequences and in short rather than long mononucleotides runs. Based on DNA sequence motifs, we propose two distinct mechanisms for generating single base deletions in vivo. Collectively, the results indicate that elevated dCTP and dTTP pools increase mismatch formation and decrease error correction across the nuclear genome, and most strongly increases mutation rates in coding and late replicating sequences.
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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.