ArticleGenetics2014
DNA replication error-induced extinction of diploid yeast.
Article in Genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Prognostic significance of POLE proofreading mutations in endometrial cancer.Journal of the National Cancer Institute · 2015Pooled it
- Towards evolutionary guided precision medicine of acute myeloid leukemia and Fanconi anemia associated bone marrow failure.Stem cells translational medicine · 2026Article
- The hidden costs of imperfection: transcription errors in protein aggregation diseases.Current opinion in genetics & development · 2025Review
- Evidence that DNA polymerase δ proofreads errors made by DNA polymerase α across the Saccharomyces cerevisiae nuclear genome.DNA repair · 2024Article
- Error-induced extinction in a multi-type critical birth-death process.Journal of mathematical biology · 2024Article
- Signification and Application of Mutator and Antimutator Phenotype-Induced Genetic Variations in Evolutionary Adaptation and Cancer Therapeutics.Journal of microbiology (Seoul, Korea) · 2023Review
- Article
- Recent Advances in Directed Yeast Genome Evolution.Journal of fungi (Basel, Switzerland) · 2022Review
- How asymmetric DNA replication achieves symmetrical fidelity.Nature structural & molecular biology · 2021Article
- Rate volatility and asymmetric segregation diversify mutation burden in cells with mutator alleles.Communications biology · 2021Article
- Distinctive genomic characteristics inAnnals of translational medicine · 2021Article
- DNA Polymerases at the Eukaryotic Replication Fork Thirty Years after: Connection to Cancer.Cancers · 2020Review
- Mismatch repair and DNA polymerase δ proofreading prevent catastrophic accumulation of leading strand errors in cells expressing a cancer-associated DNA polymerase ϵ variant.Nucleic acids research · 2020Article
- The evolution of metapopulation dynamics and the number of stem cells in intestinal crypts and other tissue structures in multicellular bodies.Evolutionary applications · 2020Review
- Article
- A PoleP286R mouse model of endometrial cancer recapitulates high mutational burden and immunotherapy response.JCI insight · 2020Article
- DNA polymerase δ proofreads errors made by DNA polymerase ε.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Splicing, genome stability and disease: splice like your genome depends on it!Current genetics · 2019Review
- Genetic Compatibility and Extensibility of Orthogonal Replication.ACS synthetic biology · 2019Article
- POLE proofreading defects: Contributions to mutagenesis and cancer.DNA repair · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Genetic defects in DNA polymerase accuracy, proofreading, or mismatch repair (MMR) induce mutator phenotypes that accelerate adaptation of microbes and tumor cells. Certain combinations of mutator alleles synergistically increase mutation rates to levels that drive extinction of haploid cells. The maximum tolerated mutation rate of diploid cells is unknown. Here, we define the threshold for replication error-induced extinction (EEX) of diploid Saccharomyces cerevisiae. Double-mutant pol3 alleles that carry mutations for defective DNA polymerase-δ proofreading (pol3-01) and accuracy (pol3-L612M or pol3-L612G) induce strong mutator phenotypes in heterozygous diploids (POL3/pol3-01,L612M or POL3/pol3-01,L612G). Both pol3-01,L612M and pol3-01,L612G alleles are lethal in the homozygous state; cells with pol3-01,L612M divide up to 10 times before arresting at random stages in the cell cycle. Antimutator eex mutations in the pol3 alleles suppress this lethality (pol3-01,L612M,eex or pol3-01,L612G,eex). MMR defects synergize with pol3-01,L612M,eex and pol3-01,L612G,eex alleles, increasing mutation rates and impairing growth. Conversely, inactivation of the Dun1 S-phase checkpoint kinase suppresses strong pol3-01,L612M,eex and pol3-01,L612G,eex mutator phenotypes as well as the lethal pol3-01,L612M phenotype. Our results reveal that the lethal error threshold in diploids is 10 times higher than in haploids and likely determined by homozygous inactivation of essential genes. Pronounced loss of fitness occurs at mutation rates well below the lethal threshold, suggesting that mutator-driven cancers may be susceptible to drugs that exacerbate replication errors.
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.