Unique molecular mechanisms for maintenance and alteration of genetic information in the budding yeast Saccharomyces cerevisiae

The high-fidelity transmission of genetic information is crucial for the survival of organisms, the cells of which have the ability to protect DNA against endogenous and environmental agents, including reactive oxygen species (ROS), ionizing radiation, and various chemical compounds. The basis of protection mechanisms has been evolutionarily conserved from yeast to humans; however, each organism often has a specialized mode of regulation that uses different sets of machineries, particularly in lower eukaryotes. The divergence of molecular mechanisms among related organisms has provided insights into the evolution of cellular machineries to a higher architecture. Uncommon characteristics of machineries may also contribute to the development of new applications such as drugs with novel mechanisms of action. In contrast to the cellular properties for maintaining genetic information, living organisms, particularly microbes, inevitably undergo genetic alterations in order to adapt to environmental conditions. The maintenance and alteration of genetic information may be inextricably linked to each other. In this review, we describe recent findings on the unconventional molecular mechanisms of DNA damage response and DNA double-strand break (DSB) repair in the budding yeast Saccharomyces cerevisiae. We also introduce our previous research on genetic and phenotypic instabilities observed in a clonal population of clinically-derived S. cerevisiae. The molecular mechanisms of this case were associated with mutations to generate tyrosine-inserting tRNA-Tyr ochre suppressors and the position effects of mutation frequencies among eight tRNA-Tyr loci dispersed in the genome. Phenotypic variations among different strain backgrounds have also been observed by another type of nonsense suppressor, the aberrant form of the translation termination factor. Nonsense suppressors are considered to be responsible for the genome-wide translational readthrough of termination codons, including natural nonsense codons. The nonsense suppressor-mediated acquisition of phenotypic variations may be advantageous for adaptation to environmental conditions and survival during evolution.