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. 1973 Sep;115(3):889–896. doi: 10.1128/jb.115.3.889-896.1973

Inhibitors of Ribonucleic Acid Synthesis in Saccharomyces cerevisiae: Decay Rate of Messenger Ribonucleic Acid

T Tønnesen 1, J D Friesen 1
PMCID: PMC246333  PMID: 4580571

Abstract

Daunomycin and ethidium bromide, two deoxyribonucleic acid-intercalating drugs, inhibit ribonucleic acid (RNA) and protein synthesis in Saccharomyces cerevisiae. Both agents rapidly curtail uptake of radioactive adenine, whereas the kinetics of radioactive leucine uptake after drug addition are consistent with translation of a pool of exponentially decaying messenger RNA. Messenger RNA half-life determinations from these experiments gave identical results over a range of drug concentrations; this value is 21 ± 4 min at 30 C. In a temperature-sensitive mutant in which RNA synthesis is curtailed at the nonpermissive temperature, a similar half-life for messenger RNA decay is found both in the absence and in the presence of either drug. This indicates that at the concentrations used in this study, neither daunomycin nor ethidium bromide has an appreciable direct effect on translation and do not increase the lability of messenger RNA.

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Selected References

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

  1. Brunschede H., Bremer H. Synthesis and breakdown of proteins in Escherichia coli during amino-acid starvation. J Mol Biol. 1971 Apr 14;57(1):35–57. doi: 10.1016/0022-2836(71)90118-5. [DOI] [PubMed] [Google Scholar]
  2. CALENDI E., DIMARCO A., REGGIANI M., SCARPINATO B., VALENTINI L. ON PHYSICO-CHEMICAL INTERACTIONS BETWEEN DAUNOMYCIN AND NUCLEIC ACIDS. Biochim Biophys Acta. 1965 May 11;103:25–49. doi: 10.1016/0005-2787(65)90539-3. [DOI] [PubMed] [Google Scholar]
  3. Chandra P., Zunino F., Götz A., Gericke D., Thorbeck R., Di Marco A. Specific inhibition of DNA-polymerases from RNA tumor viruses by some new daunomycin derivatives. FEBS Lett. 1972 Apr 1;21(3):264–268. doi: 10.1016/0014-5793(72)80179-0. [DOI] [PubMed] [Google Scholar]
  4. Cohen A., Harley E. H., Rees K. R. Antiviral effect of daunomycin. Nature. 1969 Apr 5;222(5188):36–38. doi: 10.1038/222036a0. [DOI] [PubMed] [Google Scholar]
  5. Dano K., Frederiksen S., Hellung-Larsen P. Inhibition of DNA and RNA synthesis by daunorubicin in sensitive and resistant Ehrlich ascites tumor cells in vitro. Cancer Res. 1972 Jun;32(6):1307–1314. [PubMed] [Google Scholar]
  6. Di Marco A., Silvestrini R., Di Marco S., Dasdia T. Inhibiting effect of the new cytotoxic antibiotic daunomycin on nucleic acids and mitotic activity of HeLa cells. J Cell Biol. 1965 Dec;27(3):545–550. doi: 10.1083/jcb.27.3.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fukuhara H., Kujawa C. Selective inhibition of the in vivo transcription of mitochondrial DNA by ethidium bromide and by acriflavin. Biochem Biophys Res Commun. 1970 Nov 25;41(4):1002–1008. doi: 10.1016/0006-291x(70)90184-1. [DOI] [PubMed] [Google Scholar]
  8. Geiduschek E. P., Haselkorn R. Messenger RNA. Annu Rev Biochem. 1969;38:647–676. doi: 10.1146/annurev.bi.38.070169.003243. [DOI] [PubMed] [Google Scholar]
  9. Goldring E. S., Grossman L. I., Krupnick D., Cryer D. R., Marmur J. The petite mutation in yeast. Loss of mitochondrial deoxyribonucleic acid during induction of petites with ethidium bromide. J Mol Biol. 1970 Sep 14;52(2):323–335. doi: 10.1016/0022-2836(70)90033-1. [DOI] [PubMed] [Google Scholar]
  10. Hartwell L. H., Hutchison H. T., Holland T. M., McLaughlin C. S. The effect of cycloheximide upon polyribosome stability in two yeast mutants defective respectively in the initiation of polypeptide chains and in messenger RNA synthesis. Mol Gen Genet. 1970;106(4):347–361. doi: 10.1007/BF00324052. [DOI] [PubMed] [Google Scholar]
  11. Hartwell L. H. Macromolecule synthesis in temperature-sensitive mutants of yeast. J Bacteriol. 1967 May;93(5):1662–1670. doi: 10.1128/jb.93.5.1662-1670.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hartwell L. H., McLaughlin C. S. A mutant of yeast apparently defective in the initiation of protein synthesis. Proc Natl Acad Sci U S A. 1969 Feb;62(2):468–474. doi: 10.1073/pnas.62.2.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hirschman S. Z. Inhibitors of DNA polymerases of murine leukemia viruses: activity of ethidium bromide. Science. 1971 Jul 30;173(3995):441–443. doi: 10.1126/science.173.3995.441. [DOI] [PubMed] [Google Scholar]
  14. Hutchison H. T., Hartwell L. H., McLaughlin C. S. Temperature-sensitive yeast mutant defective in ribonucleic acid production. J Bacteriol. 1969 Sep;99(3):807–814. doi: 10.1128/jb.99.3.807-814.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Johnson R. Characterization of messenger-like ribonucleic acid from Saccharomyces cerevisiae by the use of chromatography on methylated albumin-kieselguhr. Biochem J. 1970 Oct;119(4):699–706. doi: 10.1042/bj1190699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. KERRIDGE D. The effect of actidione and other antifungal agents on nucleic acid and protein synthesis in Saccharomyces carlsbergensis. J Gen Microbiol. 1958 Dec;19(3):497–506. doi: 10.1099/00221287-19-3-497. [DOI] [PubMed] [Google Scholar]
  17. KERSTEN W., KERSTEN H. DIE BINDUNG VON DAUNOMYCIN, CINERUBIN UND CHROMOMYCIN A3 AN NUCLEINSAEUREN. Biochem Z. 1965 Feb 8;341:174–183. [PubMed] [Google Scholar]
  18. Kersten W., Kersten H., Szybalski W. Physicochemical properties of complexes between deoxyribonucleic acid and antibiotics which affect ribonucleic acid synthesis (actinomycin, daunomycin, cinerubin, nogalamycin, chormomycin, mithramycin, and olivomycin). Biochemistry. 1966 Jan;5(1):236–244. doi: 10.1021/bi00865a031. [DOI] [PubMed] [Google Scholar]
  19. Khan N. A., Eaton N. R. Genetic control of maltase formation in yeast. I. Strains producing high and low basal levels of enzyme. Mol Gen Genet. 1971;112(4):317–322. doi: 10.1007/BF00334433. [DOI] [PubMed] [Google Scholar]
  20. LEVINTHAL C., KEYNAN A., HIGA A. Messenger RNA turnover and protein synthesis in B. subtilis inhibited by actinomycin D. Proc Natl Acad Sci U S A. 1962 Sep 15;48:1631–1638. doi: 10.1073/pnas.48.9.1631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lacroute F., Stent G. S. Peptide chain growth of -galactosidase in Escherichia coli. J Mol Biol. 1968 Jul 14;35(1):165–173. doi: 10.1016/s0022-2836(68)80044-0. [DOI] [PubMed] [Google Scholar]
  22. Lee S. Y., Krsmanovic V., Brawerman G. Initiation of polysome formation in mouse sarcoma 180 ascites cells. Utilization of cytoplasmic messenger ribonucleic acid. Biochemistry. 1971 Mar 2;10(5):895–900. doi: 10.1021/bi00781a026. [DOI] [PubMed] [Google Scholar]
  23. Leick V. Growth rate dependency of protein and nucleic acid composition of Tetrahymena pyriformis and the control of synthesis of ribosomal and transfer RNA. C R Trav Lab Carlsberg. 1967;36(7):113–126. [PubMed] [Google Scholar]
  24. Meyer R. R., Simpson M. V. DNA biosynthesis in mitochondria. Differential inhibition of mitochondrial and nuclear DNA polymerases by the mutagenic dyes ethidium bromide and acriflavin. Biochem Biophys Res Commun. 1969 Jan 27;34(2):238–244. doi: 10.1016/0006-291x(69)90637-8. [DOI] [PubMed] [Google Scholar]
  25. NEWTON B. A. The mode of action of phenanthridines: the effect of ethidium bromide on cell division and nucleic acid synthesis. J Gen Microbiol. 1957 Dec;17(3):718–730. doi: 10.1099/00221287-17-3-718. [DOI] [PubMed] [Google Scholar]
  26. Rusconi A., Calendi E. Action of daunomycin on nucleic acid metabolism in HeLa cells. Biochim Biophys Acta. 1966 May 19;119(2):413–415. doi: 10.1016/0005-2787(66)90201-2. [DOI] [PubMed] [Google Scholar]
  27. Slonimski P. P., Perrodin G., Croft J. H. Ethidium bromide induced mutation of yeast mitochondria: complete transformation of cells into respiratory deficient non-chromosomal "petites". Biochem Biophys Res Commun. 1968 Feb 15;30(3):232–239. doi: 10.1016/0006-291x(68)90440-3. [DOI] [PubMed] [Google Scholar]
  28. Stanners C. P. Polyribosomes of hamster cells: transit time measurements. Biophys J. 1968 Feb;8(2):231–251. doi: 10.1016/S0006-3495(68)86487-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. TOMCHICK R., MANDEL H. G. BIOCHEMICAL EFFECTS OF ETHIDIUM BROMIDE IN MICRO-ORGANISMS. J Gen Microbiol. 1964 Aug;36:225–236. doi: 10.1099/00221287-36-2-225. [DOI] [PubMed] [Google Scholar]
  30. Thomas D. Y., Williamson D. H. Products of mitochondrial protein synthesis in yeast. Nature. 1971 Oct 13;233(5320):196–199. [PubMed] [Google Scholar]
  31. Vessey D. A., Keck K. Metabolically induced shifts in the translational efficiency of yeast spheroplast polysomes. Biochemistry. 1970 Jul 7;9(14):2923–2930. doi: 10.1021/bi00816a026. [DOI] [PubMed] [Google Scholar]
  32. Ward D. C., Reich E., Goldberg I. H. Base specificity in the interaction of polynucleotides with antibiotic drugs. Science. 1965 Sep 10;149(3689):1259–1263. doi: 10.1126/science.149.3689.1259. [DOI] [PubMed] [Google Scholar]
  33. Waring M. Variation of the supercoils in closed circular DNA by binding of antibiotics and drugs: evidence for molecular models involving intercalation. J Mol Biol. 1970 Dec 14;54(2):247–279. doi: 10.1016/0022-2836(70)90429-8. [DOI] [PubMed] [Google Scholar]
  34. Wehr C. T., Parks L. W. Macromolecular synthesis in Saccharomyces cerevisiae in different growth media. J Bacteriol. 1969 May;98(2):458–466. doi: 10.1128/jb.98.2.458-466.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wolfe A. D., Allison R. G., Hahn F. E. Labilizing action of intercalating drugs and dyes on bacterial ribosomes. Biochemistry. 1972 Apr 25;11(9):1569–1572. [PubMed] [Google Scholar]

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