Mutators in Saccharomyces cerevisiae: MUT1-1, MUT1-2 and MUT2-1

Area of Science:

• Yeast genetics
• Molecular biology
• Mutation research

Background:

• Mutator strains in yeast are crucial for understanding DNA repair and mutagenesis.
• Characterizing novel mutator mutations helps elucidate genetic instability mechanisms.

Purpose of the Study:

• To characterize two yeast mutator stocks selected for high spontaneous reversion rates of the lys1-1 ochre nonsense allele.
• To identify and map the genetic loci responsible for mutator phenotypes.

Main Methods:

• Induction and selection of yeast mutator stocks.
• Spontaneous reversion rate analysis of specific alleles (lys1-1, arg4-17, his1-7).
• Tetrad analysis and complementation tests to map mutator loci.
• Assessing mutation rates at nonsense suppressor (SUP) loci and ochre alleles.

Main Results:

• Stock VA-3 harbors a single mutation, mut1-1, increasing reversion rates of ochre alleles.
• Stock VA-105 contains two loosely linked mutations: mut1-2 (at the mut1 locus) and mut2-1.
• Mutations mut1-1 and mut1-2 increase mutation rates at ochre nonsense suppressor loci but decrease rates at ochre alleles.
• Mutant mut2-1 affects both the lys1-1 site and its suppressors, with varying efficiency on missense and frameshift mutations.

Conclusions:

• Identified three recessive mutator mutations (mut1-1, mut1-2, mut2-1) in yeast with distinct effects on mutation rates.
• mut1 mutations specifically impact ochre nonsense alleles and their suppressors.
• mut2-1 exhibits a broader mutator effect, influencing both alleles and suppressors.