Mitochondria-mediated nuclear mutator phenotype in Saccharomyces cerevisiae

Anne Karin Rasmussen, Aditi Chatterjee, Lene Juel Rasmussen, Keshav K. Singh

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Using Saccharomyces cerevisiae as a model organism, we analyzed the consequences of disrupting mitochondrial function on mutagenesis of the nuclear genome. We measured the frequency of canavanine-resistant colonies as a measure of nuclear mutator phenotype. Our data suggest that mitochondrial dysfunction leads to a nuclear mutator phenotype (i) when oxidative phosphorylation is blocked in wild-type yeast at mitochondrial complex III by antimycin A and (ii) in mutant strains lacking the entire mitochondrial genome (rho0) or those with deleted mitochondrial DNA (rho-). The nuclear mutation frequencies obtained for antimycin A-treated cells as AMI as for rho- and rho0 cells were ∼2- to 3-fold higher compared to untreated control and wild-type cells, respectively. Blockage of oxidative phosphorylation by antimycin A treatment led to increased intracellular levels of reactive oxygen species (ROS). In contrast, inactivation of mitochondrial activity (rho- and rho0) led to decreased intracellular levels of ROS. We also demonstrate that in rho0 cells the REV1, REV3 and REV7 gene products, all implicated in error-prone translesion DNA synthesis (TLS), mediate mutagenesis in the nuclear genome. However, TLS was not involved in nuclear DNA mutagenesis caused by inhibition of mitochondrial function by antimycin A. Together, our data suggest that mitochondrial dysfunction is mutagenic and multiple pathways are involved in this nuclear mutator phenotype.

Original languageEnglish (US)
Pages (from-to)3909-3917
Number of pages9
JournalNucleic acids research
Volume31
Issue number14
DOIs
StatePublished - Jul 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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