Induction of the cytoplasmic petite mutation in Saccharomyces cerevisiae by the antibacterial antibiotics erythromycin and chloramphenicol (original) (raw)
Summary
Low concentrations of erythromycin and chloramphenicol (≤0.3 mg/ml) specifically affect intra-mitochondrial protein synthesis in most strains of Saccharomyces cerevisiae, thereby preventing growth on non-fermentable substrates. This effect is reversible, the genetic capacity for respiration in the absence of the drug being unaffected. However, we now show that exposure of growing cells to high concentrations (1.3–3.0 mg/ml) of either antibiotic generates a high frequency of cytoplasmic petite (respiratory-deficient) mutants with a concomitant loss of the cytoplasmic genetic determinant for respiration known as the rho factor. In one strain in which the effect of erythromycin was examined, the entire population abruptly underwent mutation but only after exposure to the drug for several generations. Mitochondrial DNA was synthesised normally during the silent pre-mutational period, but was rapidly lost, by a process partly dependent on degradation, at the time of the mutational event. Intra-mitochondrial protein synthesis was inhibited only about 67% by the lower levels of erythromycin but was completely (99%) inhibited by the higher petite-inducing levels. These results are interpreted as evidence that the normal maintenance of mitochondrial DNA in this organism requires a protein(s) whose assembly in the mitochondria is completely blocked only by high erythromycin concentrations. This protein is normally present in excess and on exposure to high drug levels replication of mitochondrial DNA is unaffected until the supply runs out. When this happens, replication ceases, existing molecules are degraded, and rho factors are destroyed.
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Authors and Affiliations
- National Institute for Medical Research, Mill Hill, London
D. H. Williamson, N. G. Maroudas & D. Wilkie - Department of Botany and Microbiology, University College, London
D. H. Williamson, N. G. Maroudas & D. Wilkie
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- D. H. Williamson
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Communicated by R. Pritchard
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Williamson, D.H., Maroudas, N.G. & Wilkie, D. Induction of the cytoplasmic petite mutation in Saccharomyces cerevisiae by the antibacterial antibiotics erythromycin and chloramphenicol.Molec. Gen. Genet. 111, 209–223 (1971). https://doi.org/10.1007/BF00433106
- Received: 13 April 1971
- Issue Date: September 1971
- DOI: https://doi.org/10.1007/BF00433106