Previously, we found evidence for a mutator phenotype associated with advancing replicative age in a common lab strain of the budding yeast, Saccharomyces cerevisiae. Pedigree analysis revealed that old cells begin to produce offspring that have dramatically higher incidences of genomic instability, which is manifest as an apparent ∼100-fold increase in LOH on at least two different chromosomes [11]. Virtually all the LOH occurred via mitotic recombination and gave rise to UPD genotypes. Subsequent analysis revealed that these LOH events were a consequence of loss of mitochondrial DNA in daughter cells, which led to a transient “crisis” state characterized by cell cycle arrest and high mortality [12]. Cells that survived this crisis showed a high frequency of LOH events in their nuclear genome.
