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Yeast mutants sensitive to trimethoprim.

J C Game, J G Little, R H Haynes

    Mutation Research
    |May 1, 1975
    PubMed
    Summary
    This summary is machine-generated.

    A Saccharomyces cerevisiae mutant sensitive to trimethoprim was identified, linked to DNA repair genes RAD6 and RAD18. This trimethoprim sensitivity arose from mutations in these specific DNA repair pathways, not simple gene reversion.

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    Area of Science:

    • Microbiology
    • Genetics
    • Molecular Biology

    Background:

    • Wild-type Saccharomyces cerevisiae (baker's yeast) exhibit resistance to growth inhibition by trimethoprim, a folate antagonist.
    • A novel mutant strain demonstrating sensitivity to trimethoprim was isolated and characterized.

    Purpose of the Study:

    • To investigate the genetic basis of trimethoprim sensitivity in Saccharomyces cerevisiae.
    • To determine the relationship between trimethoprim sensitivity and radiation sensitivity in yeast mutants.

    Main Methods:

    • Isolation and characterization of trimethoprim-sensitive yeast mutants.
    • Genetic analysis, including allelism tests with known radiation-sensitive (rad) mutants.
    • Phenotypic analysis of trimethoprim-resistant outgrowths for UV sensitivity and genetic basis.

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    Main Results:

    • The isolated trimethoprim-sensitive mutant was allelic to rad 6-1, a known radiation-sensitive gene.
    • Mutants with alleles of RAD6 and RAD18 conferred trimethoprim sensitivity, while other rad mutants were resistant.
    • Trimethoprim-sensitive strains frequently produced trimethoprim-resistant outgrowths, resulting from new mutations at different loci.

    Conclusions:

    • Trimethoprim sensitivity in Saccharomyces cerevisiae is specifically linked to mutations in the RAD6 and RAD18 DNA repair pathways.
    • The development of trimethoprim resistance in sensitive strains occurs through forward mutations in unlinked genes.
    • This study highlights a connection between folate antagonism and DNA repair mechanisms in yeast.