Skip to main content

Contribution of the Yeast Saccharomyces cerevisiae Model to Understand the Mechanisms of Selenium Toxicity

  • Chapter
  • First Online:
Selenium

Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

Abstract

Selenium (Se) is an essential trace element for mammals. It is involved in redox functions as the amino acid selenocysteine, translationally inserted in the active site of a few proteins. However, at high doses it is toxic and the mechanisms underlying this toxicity are poorly understood. Because of the high level of conservation of its genes and pathways with those of higher organisms and the powerful genetic techniques that it offers, Saccharomyces cerevisiae is an attractive model organism to study the molecular basis of Se toxicity. High-throughput technologies developed in this yeast include genome-wide screening of bar-coded systematic deletion sets, as well as whole-transcriptome, -proteome, and -metabolome analysis.

This chapter focuses on the contribution of S. cerevisiae to the understanding of the mechanisms of selenocompound toxicity, combining results from classical biochemistry with genome-wide analyses and more detailed gene-by-gene approaches. Experimental data demonstrate that toxicity is compound specific. Inorganic Se induces DNA damage whereas selenoamino acids cause proteotoxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Arnaudguilhem C, Bierla K, Ouerdane L, Preud'homme H, Yiannikouris A, Lobinski R. Selenium metabolomics in yeast using complementary reversed-phase/hydrophilic ion interaction (HILIC) liquid chromatography-electrospray hybrid quadrupole trap/Orbitrap mass spectrometry. Anal Chim Acta. 2012;757:26–38.

    Article  CAS  Google Scholar 

  • Balasubramanian B, Pogozelski WK, Tullius TD. DNA strand breaking by the hydroxyl radical is governed by the accessible surface areas of the hydrogen atoms of the DNA backbone. Proc Natl Acad Sci U S A. 1998;95:9738–43.

    Article  CAS  Google Scholar 

  • Bierla K, Bianga J, Ouerdane L, Szpunar J, Yiannikouris A, Lobinski R. A comparative study of the Se/S substitution in methionine and cysteine in Se-enriched yeast using an inductively coupled plasma mass spectrometry (ICP MS)-assisted proteomics approach. J Proteome. 2013;87:26–39.

    Article  CAS  Google Scholar 

  • Birrell GW, Brown JA, Wu HI, Giaever G, Chu AM, Davis RW, Brown JM. Transcriptional response of Saccharomyces cerevisiae to DNA-damaging agents does not identify the genes that protect against these agents. Proc Natl Acad Sci U S A. 2002;99:8778–83.

    Article  CAS  Google Scholar 

  • Björnstedt M, Kumar S, Björkhem L, Spyrou G, Holmgren A. Selenium and the thioredoxin and glutaredoxin systems. Biomed Environ Sci. 1997;10:271–9.

    PubMed  Google Scholar 

  • Böck A, Forchhammer K, Heider J, Baron C. Selenoprotein synthesis: an expansion of the genetic code. Trends Biochem Sci. 1991;16:463–7.

    Article  Google Scholar 

  • Bockhorn J, Balar B, He D, Seitomer E, Copeland PR, Kinzy TG. Genome-wide screen of Saccharomyces cerevisiae null allele strains identifies genes involved in selenomethionine resistance. Proc Natl Acad Sci U S A. 2008;105:17682–7.

    Article  CAS  Google Scholar 

  • Boiteux S, Guillet M. Abasic sites in DNA: repair and biological consequences in Saccharomyces cerevisiae. DNA Repair (Amst). 2004;3:1–12.

    Article  CAS  Google Scholar 

  • Botstein D, Fink GR. Yeast: an experimental organism for 21st century biology. Genetics. 2011;189:695–704.

    Article  CAS  Google Scholar 

  • Brozmanová J, Mániková D, Vlcková V, Chovanec M. Selenium: a double-edged sword for defense and offence in cancer. Arch Toxicol. 2010;84:919–38.

    Article  Google Scholar 

  • Chalissery J, Jalal D, Al-Natour Z, Hassan AH. Repair of oxidative DNA damage in Saccharomyces cerevisiae. DNA Repair (Amst). 2017;51:2–13.

    Article  CAS  Google Scholar 

  • Chaudiere J, Courtin O, Leclaire J. Glutathione oxidase activity of selenocystamine: a mechanistic study. Arch Biochem Biophys. 1992;296:328–36.

    Article  CAS  Google Scholar 

  • Cherest H, Davidian JC, Thomas D, Benes V, Ansorge W, Surdin-Kerjan Y. Molecular characterization of two high affinity sulfate transporters in Saccharomyces cerevisiae. Genetics. 1997;145:627–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Colombani F, Cherest H, de Robichon-Szulmajster H. Biochemical and regulatory effects of methionine analogues in Saccharomyces cerevisiae. J Bacteriol. 1975;122:375–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cupp-Sutton K, Ashby M. Biological chemistry of hydrogen selenide. Antioxidants. 2016;5:42.

    Article  Google Scholar 

  • Dimkovikj A, Fisher B, Hutchison K, Van Hoewyk D. Stuck between a ROS and a hard place: analysis of the ubiquitin proteasome pathway in selenocysteine treated Brassica napus reveals different toxicities during selenium assimilation. J Plant Physiol. 2015;181:50–4.

    Article  CAS  Google Scholar 

  • Dolinski K, Botstein D. Orthology and functional conservation in eukaryotes. Annu Rev Genet. 2007;41:465–507.

    Article  CAS  Google Scholar 

  • Foiani M, Pellicioli A, Lopes M, Lucca C, Ferrari M, Liberi G, Muzi Falconi M, Plevani P. DNA damage checkpoints and DNA replication controls in Saccharomyces cerevisiae. Mutat Res. 2000;451:187–96.

    Article  CAS  Google Scholar 

  • Ganther HE. Selenotrisulfides. Formation by the reaction of thiols with selenious acid. Biochemistry. 1968;7:2898–905.

    Article  CAS  Google Scholar 

  • Ganther HE. Reduction of the selenotrisulfide derivative of glutathione to a persulfide analog by glutathione reductase. Biochemistry. 1971;10:4089–98.

    Article  CAS  Google Scholar 

  • Garberg P, Hogberg J. The role of hypoxia in selenium metabolism. Biochem Pharmacol. 1987;36:1377–9.

    Article  CAS  Google Scholar 

  • Garberg P, Stahl A, Warholm M, Hogberg J. Studies of the role of DNA fragmentation in selenium toxicity. Biochem Pharmacol. 1988;37:3401–6.

    Article  CAS  Google Scholar 

  • Gharieb MM, Gadd GM. The kinetics of 75[Se]-selenite uptake by Saccharomyces cerevisiae and the vacuolization response to high concentrations. Mycol Res. 2004;108:1415–22.

    Article  CAS  Google Scholar 

  • Herrero E, Wellinger RE. Yeast as a model system to study metabolic impact of selenium compounds. Microb Cell. 2015;2:139–49.

    Article  CAS  Google Scholar 

  • Hsieh HS, Ganther HE. Acid-volatile selenium formation catalyzed by glutathione reductase. Biochemistry. 1975;14:1632–6.

    Article  CAS  Google Scholar 

  • Izquierdo A, Casas C, Herrero E. Selenite-induced cell death in Saccharomyces cerevisiae: protective role of glutaredoxins. Microbiology. 2010;156:2608–20.

    Article  CAS  Google Scholar 

  • Jablonska E, Vinceti M. Selenium and human health: Witnessing a copernican revolution? J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2015;33:328–68.

    Article  CAS  Google Scholar 

  • Kachroo AH, Laurent JM, Yellman CM, Meyer AG, Wilke CO, Evolution MEM. Systematic humanization of yeast genes reveals conserved functions and genetic modularity. Science. 2015;348:921–5.

    Article  CAS  Google Scholar 

  • Kitahara J, Seko Y, Imura N. Possible involvement of active oxygen species in selenite toxicity in isolated rat hepatocytes. Arch Toxicol. 1993;67:497–501.

    Article  CAS  Google Scholar 

  • Kitajima T, Chiba Y. Selenomethionine metabolism and its toxicity in yeast. Biomol Concepts. 2013;4:611–6.

    Article  CAS  Google Scholar 

  • Kitajima T, Chiba Y, Jigami Y. Mutation of high-affinity methionine permease contributes to selenomethionyl protein production in Saccharomyces cerevisiae. Appl Environ Microbiol. 2010;76:6351–9.

    Article  CAS  Google Scholar 

  • Kitajima T, Jigami Y, Chiba Y. Cytotoxic mechanism of selenomethionine in yeast. J Biol Chem. 2012;287:10032–8.

    Article  CAS  Google Scholar 

  • Kolas NK, Durocher D. DNA repair: DNA polymerase zeta and Rev1 break in. Curr Biol. 2006;16:R296–9.

    Article  CAS  Google Scholar 

  • Krogh BO, Symington LS. Recombination proteins in yeast. Annu Rev Genet. 2004;38:233–71.

    Article  CAS  Google Scholar 

  • Kumar S, Björnstedt M, Holmgren A. Selenite is a substrate for calf thymus thioredoxin reductase and thioredoxin and elicits a large non-stoichiometric oxidation of NADPH in the presence of oxygen. Eur J Biochem. 1992;207:435–9.

    Article  CAS  Google Scholar 

  • Lazard M, Blanquet S, Fisicaro P, Labarraque G, Plateau P. Uptake of selenite by Saccharomyces cerevisiae involves the high and low affinity orthophosphate transporters. J Biol Chem. 2010;285:32029–37.

    Article  CAS  Google Scholar 

  • Lazard M, Ha-Duong NT, Mounie S, Perrin R, Plateau P, Blanquet S. Selenodiglutathione uptake by the Saccharomyces cerevisiae vacuolar ATP-binding cassette transporter Ycf1p. FEBS J. 2011;278:4112–21.

    Article  CAS  Google Scholar 

  • Lazard M, Dauplais M, Blanquet S, Plateau P. Trans-sulfuration pathway seleno-amino acids are mediators of selenomethionine toxicity in Saccharomyces cerevisiae. J Biol Chem. 2015;290:10741–50.

    Article  CAS  Google Scholar 

  • Lazard M, Dauplais M, Blanquet S, Plateau P. Recent advances in the mechanism of selenoamino acids toxicity in eukaryotic cells. Biomol Concepts. 2017;8:93–104.

    Article  CAS  Google Scholar 

  • Letavayová L, Vlcková V, Brozmanová J. Selenium: from cancer prevention to DNA damage. Toxicology. 2006a;227:1–14.

    Article  Google Scholar 

  • Letavayová L, Markova E, Hermanska K, Vlckova V, Vlasakova D, Chovanec M, Brozmanova J. Relative contribution of homologous recombination and non-homologous end-joining to DNA double-strand break repair after oxidative stress in Saccharomyces cerevisiae. DNA Repair (Amst). 2006b;5:602–10.

    Article  Google Scholar 

  • Letavayová L, Vlasáková D, Spallholz JE, Brozmanová J, Chovanec M. Toxicity and mutagenicity of selenium compounds in Saccharomyces cerevisiae. Mutat Res. 2008a;638:1–10.

    Article  Google Scholar 

  • Letavayová L, Vlasáková D, Vlcková V, Brozmanová J, Chovanec M. Rad52 has a role in the repair of sodium selenite-induced DNA damage in Saccharomyces cerevisiae. Mutat Res. 2008b;652:198–203.

    Article  Google Scholar 

  • Lewinska A, Bartosz G. A role for yeast glutaredoxin genes in selenite-mediated oxidative stress. Fungal Genet Biol. 2008;45:1182–7.

    Article  CAS  Google Scholar 

  • Malkowski MG, Quartley E, Friedman AE, Babulski J, Kon Y, Wolfley J, Said M, Luft JR, Phizicky EM, DeTitta GT, Grayhack EJ. Blocking S-adenosylmethionine synthesis in yeast allows selenomethionine incorporation and multiwavelength anomalous dispersion phasing. Proc Natl Acad Sci U S A. 2007;104:6678–83.

    Article  CAS  Google Scholar 

  • Maniková D, Vlasáková D, Loduhová J, Letavayová L, Vigasová D, Krascsenitsová E, Vlcková V, Brozmanová J, Chovanec M. Investigations on the role of base excision repair and non-homologous end-joining pathways in sodium selenite-induced toxicity and mutagenicity in Saccharomyces cerevisiae. Mutagenesis. 2010;25:155–62.

    Article  Google Scholar 

  • Mániková D, Vlasáková D, Letavayová L, Klobucniková V, Griac P, Chovanec M. Selenium toxicity toward yeast as assessed by microarray analysis and deletion mutant library screen: a role for DNA repair. Chem Res Toxicol. 2012;25:1598–608.

    Article  Google Scholar 

  • McDermott JR, Rosen BP, Liu Z. Jen1p: a high affinity selenite transporter in yeast. Mol Biol Cell. 2010;21:3934–41.

    Article  CAS  Google Scholar 

  • Misra S, Boylan M, Selvam A, Spallholz JE, Björnstedt M. Redox-active selenium compounds—from toxicity and cell death to cancer treatment. Nutrients. 2015;7:3536–56.

    Article  CAS  Google Scholar 

  • Nakamuro K, Yoshikawa K, Sayato Y, Kurata H, Tonomura M. Studies on selenium-related compounds. V. Cytogenetic effect and reactivity with DNA. Mutat Res. 1976;40:177–84.

    Article  CAS  Google Scholar 

  • Painter EP. The chemistry and toxicity of selenium compounds, with special reference to the selenium problem. Chem Rev. 1941;28:179–213.

    Article  CAS  Google Scholar 

  • Perez-Sampietro M, Serra-Cardona A, Canadell D, Casas C, Arino J, Herrero E. The yeast Aft2 transcription factor determines selenite toxicity by controlling the low affinity phosphate transport system. Sci Rep. 2016;6:32836.

    Article  CAS  Google Scholar 

  • Peyroche G, Saveanu C, Dauplais M, Lazard M, Beuneu F, Decourty L, Malabat C, Jacquier A, Blanquet S, Plateau P. Sodium selenide toxicity is mediated by O2-dependent DNA breaks. PLoS One. 2012;7:e36343.

    Article  CAS  Google Scholar 

  • Pinson B, Sagot I, Daignan-Fornier B. Identification of genes affecting selenite toxicity and resistance in Saccharomyces cerevisiae. Mol Microbiol. 2000;36:679–87.

    Article  CAS  Google Scholar 

  • Plateau P, Saveanu C, Lestini R, Dauplais M, Decourty L, Jacquier A, Blanquet S, Lazard M. Exposure to selenomethionine causes selenocysteine misincorporation and protein aggregation in Saccharomyces cerevisiae. Sci Rep. 2017;7:44761.

    Article  CAS  Google Scholar 

  • Prakash S, Johnson RE, Prakash L. Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu Rev Biochem. 2005;74:317–53.

    Article  CAS  Google Scholar 

  • Preud'homme H, Far J, Gil-Casal S, Lobinski R. Large-scale identification of selenium metabolites by online size-exclusion-reversed phase liquid chromatography with combined inductively coupled plasma (ICP-MS) and electrospray ionization linear trap-Orbitrap mass spectrometry (ESI-MSn). Metallomics. 2012;4:422–32.

    Article  CAS  Google Scholar 

  • Rao Y, McCooeye M, Windust A, Bramanti E, D'Ulivo A, Mester Z. Mapping of selenium metabolic pathway in yeast by liquid chromatography-Orbitrap mass spectrometry. Anal Chem. 2010;82:8121–30.

    Article  CAS  Google Scholar 

  • Rattray AJ, Strathern JN. Error-prone DNA polymerases: when making a mistake is the only way to get ahead. Annu Rev Genet. 2003;37:31–66.

    Article  CAS  Google Scholar 

  • Salin H, Fardeau V, Piccini E, Lelandais G, Tanty V, Lemoine S, Jacq C, Devaux F. Structure and properties of transcriptional networks driving selenite stress response in yeasts. BMC Genomics. 2008;9:333.

    Article  Google Scholar 

  • Seitomer E, Balar B, He D, Copeland PR, Kinzy TG. Analysis of Saccharomyces cerevisiae null allele strains identifies a larger role for DNA damage versus oxidative stress pathways in growth inhibition by selenium. Mol Nutr Food Res. 2008;52:1305–15.

    Article  CAS  Google Scholar 

  • Seko Y, Imura N. Active oxygen generation as a possible mechanism of selenium toxicity. Biomed Environ Sci. 1997;10:333–9.

    CAS  PubMed  Google Scholar 

  • Tarze A, Dauplais M, Grigoras I, Lazard M, Ha-Duong NT, Barbier F, Blanquet S, Plateau P. Extracellular production of hydrogen selenide accounts for thiol-assisted toxicity of selenite against Saccharomyces cerevisiae. J Biol Chem. 2007;282:8759–67.

    Article  CAS  Google Scholar 

  • Thomas D, Surdin-Kerjan Y. Metabolism of sulfur amino acids in Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 1997;61:503–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Turanov AA, Xu XM, Carlson BA, Yoo MH, Gladyshev VN, Hatfield DL. Biosynthesis of selenocysteine, the 21st amino acid in the genetic code, and a novel pathway for cysteine biosynthesis. Adv Nutr. 2011;2:122–8.

    Article  CAS  Google Scholar 

  • Valdiglesias V, Pasaro E, Mendez J, Laffon B. In vitro evaluation of selenium genotoxic, cytotoxic, and protective effects: a review. Arch Toxicol. 2010;84:337–51.

    Article  CAS  Google Scholar 

  • Wallenberg M, Misra S, Wasik AM, Marzano C, Björnstedt M, Gandin V, Fernandes AP. Selenium induces a multi-targeted cell death process in addition to ROS formation. J Cell Mol Med. 2014;18:671–84.

    Article  CAS  Google Scholar 

  • Weekley CM, Harris HH. Which form is that? The importance of selenium speciation and metabolism in the prevention and treatment of disease. Chem Soc Rev. 2013;42:8870–94.

    Article  CAS  Google Scholar 

  • Whiting RF, Wei L, Stich HF. Unscheduled DNA synthesis and chromosome aberrations induced by inorganic and organic selenium compounds in the presence of glutathione. Mutat Res. 1980;78:159–69.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge Prof. Sylvain Blanquet for his contribution and constant interest and encouragements over many years.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Myriam Lazard .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lazard, M., Dauplais, M., Plateau, P. (2018). Contribution of the Yeast Saccharomyces cerevisiae Model to Understand the Mechanisms of Selenium Toxicity. In: Michalke, B. (eds) Selenium. Molecular and Integrative Toxicology. Springer, Cham. https://doi.org/10.1007/978-3-319-95390-8_4

Download citation

Publish with us

Policies and ethics