ArticlePLoS genetics2011
Mutator suppression and escape from replication error-induced extinction in yeast.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Interpreting the effects of DNA polymerase variants at the structural level.Molecular oncology · 2026Article
- A transient mutational burst occurs during yeast colony development.Molecular systems biology · 2025Article
- Unraveling mutagenic processes influencing the tumor mutational patterns of individuals with constitutional mismatch repair deficiency.Nature communications · 2025Article
- The mutational landscape of Bacillus subtilis conditional hypermutators shows how proofreading skews DNA polymerase error rates.Nucleic acids research · 2025Article
- PolED: a manually curated database of functional studies of POLE and POLD1 variants reported in humans.Database : the journal of biological databases and curation · 2025Article
- 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
- Review
- Mutators Enhance Adaptive Micro-Evolution in Pathogenic Microbes.Microorganisms · 2022Review
- Systems for in vivo hypermutation: a quest for scale and depth in directed evolution.Current opinion in chemical biology · 2021Review
- Article
- Article
- DNA Polymerases at the Eukaryotic Replication Fork Thirty Years after: Connection to Cancer.Cancers · 2020Review
- Article
- POLE Mutation Spectra Are Shaped by the Mutant Allele Identity, Its Abundance, and Mismatch Repair Status.Molecular cell · 2020Article
- A spontaneous mutation in DNA polymerase POL3 during in vitro passaging causes a hypermutator phenotype in Cryptococcus species.DNA repair · 2020Article
- POLE proofreading defects: Contributions to mutagenesis and cancer.DNA repair · 2019Review
- Probing pathways of adaptation with continuous evolution.Current opinion in systems biology · 2019Article
- Defining the impact of mutation accumulation on replicative lifespan in yeast using cancer-associated mutator phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Scalable, Continuous Evolution of Genes at Mutation Rates above Genomic Error Thresholds.Cell · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
Abstract
Cells rely on a network of conserved pathways to govern DNA replication fidelity. Loss of polymerase proofreading or mismatch repair elevates spontaneous mutation and facilitates cellular adaptation. However, double mutants are inviable, suggesting that extreme mutation rates exceed an error threshold. Here we combine alleles that affect DNA polymerase δ (Pol δ) proofreading and mismatch repair to define the maximal error rate in haploid yeast and to characterize genetic suppressors of mutator phenotypes. We show that populations tolerate mutation rates 1,000-fold above wild-type levels but collapse when the rate exceeds 10⁻³ inactivating mutations per gene per cell division. Variants that escape this error-induced extinction (eex) rapidly emerge from mutator clones. One-third of the escape mutants result from second-site changes in Pol δ that suppress the proofreading-deficient phenotype, while two-thirds are extragenic. The structural locations of the Pol δ changes suggest multiple antimutator mechanisms. Our studies reveal the transient nature of eukaryotic mutators and show that mutator phenotypes are readily suppressed by genetic adaptation. This has implications for the role of mutator phenotypes in cancer.
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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.