Summary
Some characteristic details of mutagenesis by Berenil, a non-intercalating trypanocidal dye, that govern the change from wild type (ϱ+) to vegetative petite (ϱ−) in Saccharomyces cerevisiae are presented and contrasted with the intercalating mutagens ethidium bromide and euflavine.
The extent and rate of mutagenesis by Berenil is affected by a variety of parameters controlling the cellular and mitochondrial phenotype: among them are exposure to 45°; competition with EB but not euflavine; a requirement for an energy source during and subsequent to exposure to the mutagen; exposure to caffeine; and the presence of genetic blocks in various steps of the mitochondrial repair system for uv-induced lesions. It is, however, insensitive to exposure to Antimycin A. Except for the first of these observations, qualitative differences have emerged between the responses induced by Berenil and the other mutagens, especially ethidium bromide.
Using these observations we have postulated a stepwise sequence of events that can account for the mutagenic action of Berenil.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Allen, N. E., MacQuillan, A. M.: Target analysis of mitochondrial genetic units in yeast. J. Bact. 97, 1142–1148 (1969).
Borst, P.: Mitochondrial nucleic acids. Ann. Rev. Biochem. 41, 333–376 (1972).
Ephrussi, B., Jakob, H., Grandchamp, S.: Etudes sur la suppressivité des mutants a deficiencies respiratoire de la levure. III. Etapes de la mutation grande en petite provoquée par le facteur suppressif. Genetics 54, 1–29 (1966).
Harm, W.: Differential effects of acriflavin and caffeine on various ultraviolet-irradiated Escherichia coli strains and T1 phage. Mutation Res. 4, 93–110 (1967).
Howard-Flanders, H.: DNA repair. Ann. Rev. Biochem. 37, 175–200 (1968).
Keiding, J., Westergaard, O.: Induction of DNA polymerase activity in irradiated Tetrahymena cells. Exp. Cell Res. 64, 317–322 (1971).
Krieger, N. K.: Effects of antimycin A on mutagenesis by ethidium bromide. Senior Thesis, Department of Chemistry, Indiana University (1972).
Lardy, H. A., Ferguson, S. M.: Oxidative phosphorylation in mitochondria. Ann. Rev. Biochem. 38, 991–1034 (1969).
Mahler, H. R., Mackler, B., Slonimski, P. P., Grandchamp, S.: Biochemical correlates of respiratory deficiency. II. Antigenic properties of respiratory particle. Biochemistry 3, 677–682 (1964).
Mahler, H. R., Perlman, P. S.: Effects of mutagenic treatment by ethidium bromide on cellular and mitochondrial phenotype. Arch. Biochem. Biophys. 148, 115–129 (1972a).
Mahler, H. R., Perlman, P. S.: Mutagenesis by ethidium bromide and mitochondrial membrane. J. Supramol. Structure 1, 105–124 (1972b).
Mayer, V. W.: Induction by UV-light of sectored and non-sectored petite mutants of Saccharomyces cerevisiae. Mutation Res. 9, 255–260 (1970).
Moustacchi, E.: Evidence for nucleus independent steps in control of repair of mitochondria damage. I. UV-induction of the cytoplasmic “petite” mutation in uv-sensitive nuclear mutants of Saccharomyces cerevisiae. Molec. gen. Genet. 114, 50–58 (1971).
Moustacchi, E., Enteric, S.: Differential “liquid holding recovery” for the lethal effect and cytoplasmic “petite” induction by uv light in Saccharomyces cerevisiae. Molec. gen. Genet. 109, 69–83 (1970).
Nagai, S., Nagai, H.: The interactions between caffeine, guanosine and adenosine related to the induction of respiration-deficient yeast. Nature 45, 557 (1958).
Nagai, S., Yanagashima, N., Nagai, H.: Advances in the study of the respiration-deficient mutation in yeast and other microorganisms. Bact. Rev. 25, 404–426 (1961).
Negrotti, T., Wilkie, D.: Induction of respiratory deficiency in repression of the respiratory system in a mutant of Saccharomyces cerevisiae. Biochim. biophys. Acta (Amst.) 153, 341–349 (1968).
Ogur, M., St. John, R., Nagai, S.: Tetrazolium overlay techniques for population studies of respiration deficiency in yeast. Science 125, 928–929 (1957).
Paoletti, J., Couder, H., Guerineau, M.: A yeast mitochondrial deoxyribonuclease stimulated by ethidium bromide. Biochem. biophys. Res. Commun. 48, 950–958 (1972).
Perlman, P. S.: The nature of mitochondrial gene products. Ph. Dissertation, Indiana University, 1971.
Perlman, P. S., Mahler, H. R.: Molecular consequence of ethidium bromide mutagenesis. Nature (Lond.) New Biol. 231, 12–16 (1971a).
Perlman, P. S., Mahler, H. R.: A premutational state induced in yeast by ethidium bromide. Biochem. biophys. Res. Commun. 44, 261–267 (1971b).
Setlow, R. B.: Steps in the repair of DNA in fact and fancy. Brookhaven Symp. in Biol. 20, 1–12 (1968).
Shankel, D. M.: “Mutational synergism” of ultraviolet light and caffeine in Escherichia coli. J. Bact. 84, 410–415 (1962).
Sideropoulos, A. S., Shankel, D. M.: Mechanism of caffeine enhancement of mutations induced by sublethal ultraviolet dosages. J. Bact. 96, 168–204 (1968).
Slonimski, P. P.: Reported at the International Symposium on DNA of Eukaryotes, Port Cros, France, May 5–9, 1971, and private communication.
Waring, M.: Variation of the supercoils in closed circular DNA by binding of antibiotics and drugs. Evidence for molecular models involving intercalation. J. molec. Biol. 54, 247–279 (1970).
Westergaard, O., Lindberg, P.: An induced mitochondrial DNA polymerase for Tetrahymena. Europ. J. Biochem. 28, 422–431 (1972).
Westergaard, O., Marker, K. A., Keiding, J.: Induction of a mitochondrial DNA polymerase in Tetrahymena. Nature (Lond.) 227, 709–710 (1970).
Witkin, E. M.: Modification of mutagenesis initiated by ultraviolet light through post treatment of bacteria with basic dyes. J. cell comp. Physiol., Suppl. 1, 135–144 (1961).
Witkin, E. M.: Mutation-proof and mutation-prone modes of survival in derivatives of Escherichia coli B differing in sensitivity to ultraviolet-light. Brookhaven Symp. in Biol. 20, 17–53 (1968).
Witkin, E. M., Farquharson, E. L.: Enhancement and diminution of ultraviolet-light initiated mutagenesis by post-treatment with caffeine in Escherichia coli in CIBA Foundation Symposium on Mutation as Cellular Process, ed. by Wolstenholme, E. W., and O'Connor, M., p. 37–49. London: Churchill Press 1969.
Wolstenholme, E. N., O'Connor, M.: (editors) CIBA Foundation Symposium on Mutation as Cellular Process. London: Churchill Press 1969.
Author information
Authors and Affiliations
Additional information
Communicated by Ch. Auerbach
Publication No. 2122.
Rights and permissions
About this article
Cite this article
Perlman, P.S., Mahler, H.R. Induction of respiration deficient mutants in Saccharomyces cerevisiae by Berenil. Molec. Gen. Genet. 121, 295–306 (1973). https://doi.org/10.1007/BF00433229
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00433229