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Mutation induction by excess deoxyribonucleotides in Saccharomyces cerevisiae
Basic Life Sciences
|January 1, 1985
Summary
Excess thymidylate (dTMP) is toxic and mutagenic to yeast, particularly in respiratory-deficient strains. This deoxyribonucleotide
Area of Science:
- Molecular Biology
- Yeast Genetics
- Genotoxicity Studies
Background:
- Deoxyribonucleotides (dNTPs) are essential for DNA synthesis.
- Imbalances in dNTP pools can lead to cellular toxicity and mutations.
- Thymidylate (dTMP) is a key dNTP involved in DNA replication and repair.
Purpose of the Study:
- To investigate the toxicity and mutagenicity of excess dTMP in yeast.
- To compare the genotoxic effects of dTMP with other deoxyribonucleotides.
- To identify factors influencing dTMP-induced mutagenesis.
Main Methods:
- Utilized yeast strains (831 rho+ and 833 rho) with efficient dTMP uptake.
- Assessed toxicity and mutagenicity using a forward mutation assay (CAN1 to can1).
- Exposed cells in both exponentially growing and stationary phases.
Main Results:
- Excess dTMP demonstrated toxicity and mutagenicity in exponentially growing yeast.
- The respiratory-deficient strain (833 rho) showed a tenfold increase in sensitivity to dTMP genotoxicity.
- Mutagenic effects of dTMP were minimal in stationary phase cells and in an ochre mutant.
- Other deoxyribonucleotides (dCMP, dAMP, dGMP) also exhibited mutagenic potential.
Conclusions:
- Excess dTMP poses a significant genotoxic risk to actively dividing yeast cells.
- Cellular respiration status influences sensitivity to dTMP-induced DNA damage.
- The mutagenicity of excess dTMP is dependent on cell cycle phase and specific genetic backgrounds.
- Imbalances in other deoxyribonucleotide pools may also contribute to mutagenesis.