Skip to main content
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1972 Mar;109(3):1134–1138. doi: 10.1128/jb.109.3.1134-1138.1972

Induction of Cycloheximide-Resistant Mutants in Saccharomyces cerevisiae with N-Methyl-N′-Nitro-N-Nitrosoguanidine and ICR-170

David J Brusick 1
PMCID: PMC247334  PMID: 4551745

Abstract

N-Methyl-N′-nitro-N-nitrosoguanidine (MNNG) induces cycloheximide-resistant mutations in Saccharomyces cerevisiae, but few, if any, resistant mutants are induced by the acridine mustard ICR-170. Cycloheximide sensitivity in yeast is associated with the ribosome, and treatment with the antibiotic at concentrations of 2 μg/ml results in complete inhibition of protein synthesis. Missense mutations induced by MNNG probably lead to the loss of cycloheximide binding sites on the ribosome, resulting in resistance to the antibiotic without altering the activity of the organelle in protein synthesis. ICR-170, however, induced primarily frameshift mutations that would alter ribosome structural integrity, resulting in cell death rather than resistance. ICR-170 and MNNG are both mutagenic in a system in which base-pair substitution and frameshift mutations can be detected. These results indicate that cycloheximide resistance in S. cerevisiae, like streptomycin and spectinomycin resistance in Escherichia coli, can be induced by base-pair substitution mutagens but not by frameshift mutagens such as ICR-170.

Full text

PDF
1134

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames B. N., Whitfield H. J., Jr Frameshift mutagenesis in Salmonella. Cold Spring Harb Symp Quant Biol. 1966;31:221–225. doi: 10.1101/sqb.1966.031.01.030. [DOI] [PubMed] [Google Scholar]
  2. Brusick D. J. The mutagenic acitivity of ICR-170 in Saccharomyces cerevisiae. Mutat Res. 1970 Jul;10(1):11–19. doi: 10.1016/0027-5107(70)90141-7. [DOI] [PubMed] [Google Scholar]
  3. CARLTON B. C., YANOFSKY C. Studies on the position of six amino acid substitutions in the tryptophan synthetase A protein. J Biol Chem. 1963 Jul;238:2390–2392. [PubMed] [Google Scholar]
  4. CRICK F. H., BARNETT L., BRENNER S., WATTS-TOBIN R. J. General nature of the genetic code for proteins. Nature. 1961 Dec 30;192:1227–1232. doi: 10.1038/1921227a0. [DOI] [PubMed] [Google Scholar]
  5. Cooper D., Banthorpe D. V., Wilkie D. Modified ribosomes conferring resistance to cycloheximide in mutants of Saccharomyces cerevisiae. J Mol Biol. 1967 Jun 14;26(2):347–350. doi: 10.1016/0022-2836(67)90302-6. [DOI] [PubMed] [Google Scholar]
  6. Grenson M., Mousset M., Wiame J. M., Bechet J. Multiplicity of the amino acid permeases in Saccharomyces cerevisiae. I. Evidence for a specific arginine-transporting system. Biochim Biophys Acta. 1966 Oct 31;127(2):325–338. doi: 10.1016/0304-4165(66)90387-4. [DOI] [PubMed] [Google Scholar]
  7. Guest J. R., Yanofsky C. Amino acid replacements associated with reversion and recombination within a coding unit. J Mol Biol. 1965 Jul;12(3):793–804. doi: 10.1016/s0022-2836(65)80328-x. [DOI] [PubMed] [Google Scholar]
  8. MAGNI G. E., VONBORSTEL R. C., SORA S. MUTAGENIC ACTION DURING MEIOSIS AND ANTIMUTAGENIC ACTION DURING MITOSIS BY 5-AMINOACRIDINE IN YEAST. Mutat Res. 1964 Oct;106:227–230. doi: 10.1016/0027-5107(64)90003-x. [DOI] [PubMed] [Google Scholar]
  9. Magni G E, Von Borstel R C. Different Rates of Spontaneous Mutation during Mitosis and Meiosis in Yeast. Genetics. 1962 Aug;47(8):1097–1108. doi: 10.1093/genetics/47.8.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Magni G. E., Puglisi P. P. Mutagenesis of super-suppressors in yeast. Cold Spring Harb Symp Quant Biol. 1966;31:699–704. doi: 10.1101/sqb.1966.031.01.089. [DOI] [PubMed] [Google Scholar]
  11. Munz P., Leupold U. Characterization of ICR-170-induced mutations in Schizosaccharomyces pombe. Mutat Res. 1970 Feb;9(2):199–212. doi: 10.1016/0027-5107(70)90058-8. [DOI] [PubMed] [Google Scholar]
  12. Ozaki M., Mizushima S., Nomura M. Identification and functional characterization of the protein controlled by the streptomycin-resistant locus in E. coli. Nature. 1969 Apr 26;222(5191):333–339. doi: 10.1038/222333a0. [DOI] [PubMed] [Google Scholar]
  13. Rao S. S., Grollman A. P. Cycloheximide resistance in yeast: a property of the 60s ribosomal subunit. Biochem Biophys Res Commun. 1967 Dec 15;29(5):696–704. doi: 10.1016/0006-291x(67)90273-2. [DOI] [PubMed] [Google Scholar]
  14. SIEGEL M. R., SISLER H. D. SITE OF ACTION OF CYCLOHEXIMIDE IN CELLS OF SACCHAROMYCES PASTORIANUS. I. EFFECT OF THE ANTIBIOTIC ON CELLULAR METABOLISM. Biochim Biophys Acta. 1964 May 18;87:70–82. doi: 10.1016/0926-6550(64)90048-9. [DOI] [PubMed] [Google Scholar]
  15. Siegel M. R., Sisler H. D. Site of action of cycloheximide in cells of Saccharomyces pastorianus. 3. Further studies on the mechanism of action and the mechanism of resistance in saccharomyces species. Biochim Biophys Acta. 1965 Aug 10;103(4):558–567. [PubMed] [Google Scholar]
  16. Silengo L., Schlessinger D., Mangiarotti G., Apirion D. Induction of mutations to streptomycin and spectinomycin resistance in Escherichia coli by N-methyl-N'-nitroso-N-nitroguanidine and acridine half-mustard ICR-191. Mutat Res. 1967 Sep-Oct;4(5):701–703. doi: 10.1016/0027-5107(67)90056-5. [DOI] [PubMed] [Google Scholar]
  17. WILKIE D., LEE B. K. GENETIC ANALYSIS OF ACTIDIONE RESISTANCE IN SACCHAROMYCES CEREVISIAE. Genet Res. 1965 Feb;6:130–138. doi: 10.1017/s0016672300003992. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES