DNA Repair and Mutagen Interaction in Saccharomyces: Theoretical Considerations
DNA repair pathways have been identified in the yeast Saccharomyces cerevisiae. One or more of these pathways are mutagenic, i.e., induce mutations during the process of repair of lesions in DNA. Some types of lesions in DNA require components of more than one pathway for repair.
When more than one mutagen is used in an experiment, they can interact in a variety of ways: additively, synergistically, epistatically (dominantly), or antagonistically. These are the result of the way in which mutagens cause effects on DNA repair systems or on metabolic activation or detoxification systems.
Preliminary rules are presented for interpreting the interactions of mutagens. Mutation yield will be additive or more than additive (1) if the agents compete for a nonmutagenic repair system, (2) if one of them inhibits a nonmutagenic repair system, (3) if one inactivates a metabolic inactivation system, (4) if one induces a metabolic activation system. The converse situations all reduce mutation yield.
Four pathways or systems have been identified in the yeast Saccharomyces cerevisiae which are associated with repair of lesions induced by ultraviolet radiation. Three pathways have been identified by genetic methodology, namely, by assigning each radiation-sensitive mutant to an epistasis group [1, 4, 5, 7]. The epistasis groups are called the RAD3, RAD51, and RAD18 pathways. The initial steps have been identified by (1) synergistic interaction with the presumed initial step in another epistasis group, (2) dominance of phenotype over other members of the same epistasis group, and (3) a mutator phenotype which, because of channelling of lesions into a mutagenic repair pathway, is expected for a mutant of the gene encoding the enzyme which catalyzes the initial step of a nonmutagenic repair pathway . The fourth system is the photorepair system, PHR1 .
KeywordsSaccharomyces Cerevisiae Repair Pathway Repair System Detoxification System Methyl Methanesulfonate
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