ArticleDNA repair2020
A spontaneous mutation in DNA polymerase POL3 during in vitro passaging causes a hypermutator phenotype in Cryptococcus species.
Article in DNA repair, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- 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
- Distinct evolutionary trajectories following loss of RNA interference inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Distinct evolutionary trajectories following loss of RNA interference inbioRxiv : the preprint server for biology · 2024Article
- Drivers of diversification in fungal pathogen populations.PLoS pathogens · 2024Review
- Recent insights into the evolution of mutation rates in yeast.Current opinion in genetics & development · 2022Review
- Epigenetic Regulation of Antifungal Drug Resistance.Journal of fungi (Basel, Switzerland) · 2022Review
- Molecular mechanisms underlying the emergence of polygenetic antifungal drug resistance inJAC-antimicrobial resistance · 2022Article
- Mutators Enhance Adaptive Micro-Evolution in Pathogenic Microbes.Microorganisms · 2022Review
- Functional Roles of Homologous Recombination and Non-Homologous End Joining in DNA Damage Response and Microevolution inJournal of fungi (Basel, Switzerland) · 2021Article
- The need for environmental surveillance to understand the ecology, epidemiology and impact of Cryptococcus infection in Africa.FEMS microbiology ecology · 2021Review
- Treatment strategies for cryptococcal infection: challenges, advances and future outlook.Nature reviews. Microbiology · 2021Review
- The interplay of phenotype and genotype in Cryptococcus neoformans disease.Bioscience reports · 2020Review
- Short-term evolution strategies for host adaptation and drug escape in human fungal pathogens.PLoS pathogens · 2020Review
- Advances in understanding the evolution of fungal genome architecture.F1000Research · 2020Review
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Authors and funding
4 authors.
Funding
Abstract
Passaging of microbes in vitro can lead to the selection of microevolved derivatives with differing properties to their original parent strains. One well characterised instance is the phenotypic differences observed between the series of strains derived from the type strain of the human pathogenic fungus Cryptococcus neoformans. A second case was reported in the close relative Cryptococcus deneoformans, in which a well-studied isolate ATCC 24067 (52D) altered its phenotypic characteristics after in vitro passaging in different laboratories. One of these derivatives, ATCC 24067A, has decreased virulence and also exhibits a hypermutator phenotype, in which the mutation rate is increased compared to wild type. In this study, the molecular basis behind the changes in the lineage of ATCC 24067 was determined by next-generation sequencing of the parent and passaged strain genomes. This analysis resulted in the identification of a point mutation that causes a D270G amino acid substitution within the exonuclease proofreading domain of the DNA polymerase delta subunit encoded by POL3. Complementation with POL3 confirmed that this mutation is responsible for the hypermutator phenotype of this strain. Regeneration of the mutation in C. neoformans, to eliminate the additional mutations present in the ATCC 24067A genetic background, demonstrated that the hypermutator phenotype of the pol3
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