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Studies on the induction of petite mutants in yeast by analogues of berenil

Characterization of three mutants resistant to the compound Hoe 15 030

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Summary

Compound Hoe 15 030 is an analogue of berenil which is as effective as berenil in inducing petite mutants in Saccharomyces cerevisiae. Hoe 15 030 has greater stability than berenil in aqueous solution, and is less toxic to yeast at high drug concentrations. Mutants of S. cerevisia strain J69-1B have been isolated which are resistant to the petite inducing effects of Hoe 15 030. Three mutant strains (HR7, HR8 and HR10) were characterized and each was shown to carry a recessive nuclear mutation determining resistance to Hoe 15 030. The degree of resistance to Hoe 15 030 is different for each mutant, and each was found to be co-ordinately cross-resistant both to berenil and to another analogue of berenil, Hoe 13 548. However, the three mutants show no cross-resistance to other unrelated petite inducing drugs, including ethidium bromide, euflavine and 1-methyl phenyl neutral red.

Further studies on the mutants revealed that each strain exhibits characteristic new properties indicative of changes in mitochondrial membrane functions concerned with the replication (and probably also repair) of mitochondrial DNA. Thus, mutant HR7 is hypersensitive to petite induction by the detergent sodium dodecyl sulphate under conditions where the parent J69-1B is unaffected by this agent. Mutant HR8 is even more sensitive to sodium dodecyl sulphate than is HR7, and additionally shows a markedly elevated spontaneous petite frequency. Isolated mitochondria from strains HR8 and HR10 (but not HR7) show resistance to the inhibitory effects of Hoe 15 030 on the replication of mitochondrial DNA in vitro.

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Authors and Affiliations

  1. Department of Biochemistry, Monash University, 3168, Clayton, Victoria, Australia

    Paul R. Vaughan & Phillip Nagley

  2. Pharma Synthese, Hoechst Aktiengesellschaft, Postfach 80 03 20, D-6230, Frankfurt am Main 80, Federal Republic of Germany

    H. Loewe

Authors
  1. Paul R. Vaughan
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  2. H. Loewe
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  3. Phillip Nagley
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Communicated by W. Gajewski

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Vaughan, P.R., Loewe, H. & Nagley, P. Studies on the induction of petite mutants in yeast by analogues of berenil. Molec. Gen. Genet. 172, 259–269 (1979). https://doi.org/10.1007/BF00271725

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  • DOI: https://doi.org/10.1007/BF00271725

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