Summary
A discrete class of strains of Saccharomyces cerevisiae, able to utilize, highly efficiently, exogenous deoxythymidine-5′-monophosphate (dTMP), was found to be sensitive to concentrations >10 μM dTMP in an otherwise complete growth medium. Excess dTMP is cytostatic and cytotoxic: 90% of exponentially growing cells lose colony forming ability within 1 h of exposure to excess dTMP in a growth medium. Uptake of dTMP, adenine, histidine, and leucine does occur during this thymidylate excess death (TED). dTMP is anabolized to higher phosphorylated nucleotides and catabolized to thymidine intracellularly. DNA synthesis is blocked under TED-conditions but not RNA and protein biosynthesis.
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Abbreviations
- dTMP:
-
deoxythymidine-5′-monophosphate
- dTDP:
-
deoxythymidine-5′-diphosphate
- dTTP:
-
deoxythymidine-5′-triphosphate
- dThd:
-
deoxythymidine
- tmp :
-
genetic symbol for dTMP-auxotrophy
- TMP :
-
genetic symbol for dTMP-prototrophy
- (tlr):
-
symbol for the phenotype of a yeast strain to efficiently utilize exogenous dTMP
References
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Communicated by F. Kaudewitz
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Toper, R., Fäth, W.W. & Brendel, M. Nucleic acid metabolism in yeast II. Metabolism of thymidylate during thymidylate excess death. Molec. Gen. Genet. 182, 60–64 (1981). https://doi.org/10.1007/BF00422767
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DOI: https://doi.org/10.1007/BF00422767