Skip to main content
SpringerLink
Log in

Sensitivity to Sn2+ of the Yeast Saccharomyces cerevisiae Depends on General Energy Metabolism, Metal Transport, Anti-Oxidative Defences, and DNA Repair

  • Published:
Biometals Aims and scope Submit manuscript

Abstract

Resistance to stannous chloride (SnCl2) of the yeast Saccharomyces cerevisiae is a product of several metabolic pathways of this unicellular eukaryote. Sensitivity testing of different null mutants of yeast to SnCl2 revealed that DNA repair contributes to resistance, mainly via recombinational (Rad52p) and error-prone (Rev3p) steps. Independently, the membrane transporter Atr1p/Snq1p (facilitated transport) contributed significantly to Sn2+-resistance whereas absence of ABC export permease Snq2p did not enhance sensitivity. Sensitivity of the superoxide dismutase mutants sod1 and sod2 revealed the importance of these anti-oxidative defence enzymes against Sn2+-imposed DNA damage while a catalase-deficient mutant (ctt1) showed wild type (WT) resistance. Lack of transcription factor Yap1, responsible for the oxidative stress response in yeast, led to 3-fold increase in Sn2+-sensitivity. While loss of mitochondrial DNA did not change the Sn2+-resistance phenotype in any yeast strain, cells with defect cytochrome c oxidase (CcO mutants) showed gradually enhanced sensitivities to Sn2+ and different spontaneous mutation rates. Highest sensitivity to Sn2+ was observed when yeast was in exponential growth phase under glucose repression. During diauxic shift (release from glucose repression) Sn2+-resistance increased several hundred-fold and fully respiring and resting cells were sensitive only at more than 1000-fold exposure dose, i.e. they survived better at 25 mM than exponentially growing cells at 25 μM Sn2+. This phenomenon was observed not only in WT but also in already Sn2+-sensitive rad52 as well as in sod1, sod2 and CcO mutant strains. The impact of metabolic steps in contribution to Sn2+-resistance had the following ranking: Resting WT cells > membrane transporter Snq1p > superoxide dismutases > transcription factor Yap1p ≥ DNA repair \( \gg \) exponentially growing WT cells.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alseth I, Eide L, Pirovano M, Rognes T, Seeberg E, Bjoras M (1999) The Saccharomyces cerevisiae homologues of endonuclease III from Escherichia coli, Ntg1 and Ntg2, are both required for efficient repair of spontaneous and induced oxidative DNA damage in yeast. Mol Cell Biol 19:3779–3787

    PubMed  CAS  Google Scholar 

  • Assis ML, de Mattos JC, Caceres MR et al (2002) Adaptive response to H2O2 protects against SnCl2 damage: the OxyR system involvement. Biochimie 84:291–294

    Article  PubMed  CAS  Google Scholar 

  • Barros MH, Netto LES, Kowaltowski AJ (2003) H2O2 generation in Saccharomyces cerevisiae respiratory PET mutants: effect of cytochrome C. Free Rad Biol Med 35:179–188

    Article  PubMed  CAS  Google Scholar 

  • Bernardo-Filho M, Cunha MC, Valsa JO, Caldeira-de-Araújo A, Silva FCP, Fonseca AS (1994) Evaluation of potential genotoxicity of stannous chloride: inactivation, filamentation and lysogenic induction of Escherichia coli. Food Chem Toxicol 32:477–479

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Brendel M, Revers LF, Strauss M et al (2003) The role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae. Mutat Res 544:179–193

    Article  PubMed  CAS  Google Scholar 

  • Burke D, Dawson D. Stearns T (2000) Methods in yeast genetics. Cold Spring Harbour Laboratory Course Manual, CSH Laboratory Press, N.Y

    Google Scholar 

  • Chmielnicka J, Szymanska JA, Sniec J (1981) Distribution of tin in the rat and disturbances in the metabolism of zinc and copper due to repeated exposure to SnCl2. Arch Toxicol 47:263–268

    Article  PubMed  CAS  Google Scholar 

  • Dantas FJ, Moraes MO, Carvalho EF, Valsa JO, Bernardo-Filho M, Caldeira-de-Araujo A (1996) Lethality induced by stannous chloride on Escherichia coli AB1157: participation of reactive oxygen species. Food Chem Toxicol 34:959–962

    Article  PubMed  CAS  Google Scholar 

  • Dantas FJ, Moraes MO, de Mattos JC et al. (1999) Stannous chloride mediates single strand breaks in plasmid DNA through reactive oxygen species formation. Toxicol Lett 110:129–136

    Article  PubMed  CAS  Google Scholar 

  • De Winde JH, Thevelein JM, Winderickx J (1997) From feast to famine: adaptation to nutrient depletion in yeast. In: Hohmann S, Mager WH (eds) Yeast Stress Responses. Springer, Berlin, Heidelberg, New York, pp 7–52

    Google Scholar 

  • Eide D, Guerinot ML (1997) Metal ion uptake in eukaryotes: research on Saccharomyces cerevisiae reveals complexity and insights about other species. ASM News 63:199–205

    Google Scholar 

  • Eisen JA, Hanawalt PC (1999) A phylogenomic study of DNA repair genes, proteins and processes. Mutat Res 435:171–213

    PubMed  CAS  Google Scholar 

  • Fuge EK, Werner-Washburne M (1997) Stationary phase in the yeast Saccharomyces cerevisiae. In: Hohmann S, Mager WH (eds) Yeast Stress Responses. Springer, Berlin, Heidelberg New York, pp 53–74

    Google Scholar 

  • Gömpel-Klein P, Brendel M (1990) Allelism of SNQ1 and ATR1, genes of the yeast Saccharomyces cerevisiae required for controlling sensitivity to 4-nitroquinoline-N-oxide and aminotriazole. Curr Genet 18:93–96

    Article  PubMed  Google Scholar 

  • Grant CM, Perrone G, Dawes IW (1998) Glutathione and catalase provide overlapping defenses for protection against hydrogen peroxide in the yeast Saccharomyces cerevisiae. Biochem Biophys Res Commun 253:893–898

    Article  PubMed  CAS  Google Scholar 

  • Hartig A, Ruis H (1986) Nucleotide sequence of the Saccharomyces cerevisiae CTT1 gene and deduced amino-acid sequence of yeast catalase T. Eur J Biochem 160:487–490

    Article  PubMed  CAS  Google Scholar 

  • Hattori T, Maehashi H, Miyazawa T, Naito M (2001) Potentiation by stannous chloride of calcium entry into osteoblastic MC3T3-E1 cells through voltage-dependent L-type calcium channels. Cell Calcium 30:67–72

    Article  PubMed  CAS  Google Scholar 

  • Heuchel R, Radtke F, Georgiev O, Stark G, Aguet M, Schaffner W (1994) The transcription factor MTF-1 is essential for basal and heavy metal-induced metallothionein gene expression. EMBO J 13:2870–2875

    PubMed  CAS  Google Scholar 

  • Kanazawa S, Driscoll M, Struhl K. (1988) ATR1, a Saccharomyces cerevisiae gene encoding a transmembrane protein required for aminotriazole resistance. Mol Cell Biol 8:664–673

    PubMed  CAS  Google Scholar 

  • Lawrence CW. (2002) Cellular roles of DNA polymerase ζ and Rev1 protein. DNA Repair 1:425–435

    Article  PubMed  CAS  Google Scholar 

  • Machida I, Nakai S (1980) Induction of spontaneous and UV-induced mutations during commitment to meiosis in Saccharomyces cerevisiae. Mutat Res 73:59–68

    PubMed  CAS  Google Scholar 

  • Maris AF, Assumpção ALK, Bonatto D, Brendel M, Henriques JAP (2001) Diauxic shift-induced stress resistance against hydroperoxides in Saccharomyces cerevisiae is not an adaptive stress response and does not depend on functional mitochondria. Curr Genet 39:137–149

    Article  PubMed  CAS  Google Scholar 

  • Martínez A, Urios A, Blanco M (2000) Mutagenicity of 80 chemicals in Escherichia coli tester strains IC203, deficient in OxyR, and its oxyR(+) parent WP2 uvrA/pKM101: detection of 31 oxidative mutagens. Mutat Res 467:41–53

    PubMed  Google Scholar 

  • McLean JR, Kaplan JG (1979) The effect of tin on unscheduled and semi-conservative DNA synthesis. In: Kaplan JG (ed) The Molecular Basis of Immune Cell Function. Elsevier Biomedical, Amsterdam

    Google Scholar 

  • McLean JR, Blakey DH, Douglas GR, Kaplan JR (1983a) The effect of stannous and stannic (tin) chloride on DNA in Chinese hamster ovary cells. Mutat Res 119:195–201

    Article  CAS  Google Scholar 

  • McLean JR, Birnboim HC, Pontefact R, Kaplan JG (1983b) The effect of tin chloride on the structure and function of DNA in human white blood cells. Chem Biol Interac 46:189–200

    Article  CAS  Google Scholar 

  • McMurray CT, Tainer JA (2003) Cancer, cadmium and genome integrity. Nat Genet 34:34239–34241

    Article  Google Scholar 

  • Pungartnik C, Viau C, Picada J, Caldeira-de-Araújo A, Henriques JAP, Brendel M. 2005 Genotoxicity of stannous chloride in yeast and bacteria. Mutat Res 583, 146–157

    Google Scholar 

  • Pungartnik C, Kern MF, Brendel M, Henriques JAP (1999) Mutant allele pso7-1, that sensitizes Saccharomyces cerevisiae to photoactivated psoralen, is allelic with COX11, encoding a protein indispensable for a functional cytochrome c oxidase. Curr Genet 36:124–129

    Article  PubMed  CAS  Google Scholar 

  • Salmon TB, Evert BA, Song B, Doetsch PW (2004) Biological consequences of oxidative stress-induced DNA damage in Saccharomyces cerevisiae. Nucl Acid Res 32:3712–3723

    Article  CAS  Google Scholar 

  • Schmidt CL, Grey M, Schmidt M, Brendel M, Henriques JAP (1999) Allelism of Saccharomyces cerevisiae genes PSO6, involved in survival after 3-CPs+UVA induced damage, and ERG3, encoding the enzyme sterol C-5 desaturase. Yeast 15:1503–1510

    Article  PubMed  CAS  Google Scholar 

  • Schroeder HA, Balassa JJ, Tipton IH (1964) Abnormal trace metals in man: tin. J Chron Dis 17:483–502

    Article  PubMed  CAS  Google Scholar 

  • Servos J, Haase E, Brendel M (1993) GeneSNQ2 of Saccharomyces cerevisiae, which confers resistance to 4-nitroquinoline-N-oxide and other chemicals, encodes a 169 kDa protein homologous to ATP-dependent permeases. Mol Gen Genet 236:214–218

    Article  PubMed  CAS  Google Scholar 

  • Spector D, Labarre J, Toledano MB (2001) A genetic investigation on the essential role of glutathione: mutations in the proline biosynthetic pathway are the only suppressors of glutathione auxotrophy in yeast. J Biol Chem 276:7011–7016

    Article  PubMed  CAS  Google Scholar 

  • Swanson RL, Morey NJ, Doetsch PW, Jinks-Robertson S (1999) Overlapping specificities of base excision repair, nucleotide excision repair, recombination, and translesion synthesis pathway for DNA base damage in Saccharomyces cerevisiae. Mol Cell Biol 19:2929–2935

    PubMed  CAS  Google Scholar 

  • Tomsett AB, Thurmann DA (1988) Molecular biology of metal tolerance of plants. Plant Cell Environ 11:383–394

    Article  CAS  Google Scholar 

  • Torres-Ramos CA, Johnson RE, Prakash L, Prakash S (2000) Evidence for the involvement of nucleotide excision repair in the removal of abasic sites in yeast. Mol Cell Biol 20:3522–3528

    Article  PubMed  CAS  Google Scholar 

  • Van Ho A, McVery Ward D, Kaplan J (2002) Transition metal transport in yeast. Annu Rev Microbiol 56:237–261

    Article  PubMed  Google Scholar 

  • Viau CM, Yoneama ML, Dias JF, Pungartnik C, Brendel M, Henriques JAP (2005) Detection and quantitative determination by PIXE of the mutagen Sn2+ in yeast cells. Nucl. Instrum Meth Physics Res B, in press

  • von Borstel RC, Cain KT, Steinberg CM (1971) Inheritance of spontaneous mutability in yeast. Genetics 69:17–27

    Google Scholar 

  • Wehner EP, Rao E, Brendel M (1983) Molecular structure and genetic regulation of SFA, a gene responsible for resistance to formaldehyde in Saccharomyces cerevisiae. Mol Gen Genet 237:351–358

    Google Scholar 

  • Wood MJ, Storz G, Tjandra N (2004) Structural basis for redox regulation of Yap1 transcription factor localization. Nature 430:917–921

    Article  PubMed  CAS  Google Scholar 

  • Wu A, Moye-Rowley WS (1994) GSH1, which encodes gamma-glutamylcysteine synthetase, is a target gene for yAP-1 transcriptional regulation. Mol Cell Biol 14:5832–5839

    PubMed  CAS  Google Scholar 

  • You HJ, Swanson RL, Harrington C et al. (1999) Saccharomyces cerevisiae Ntg1p and Ntg2p: broad specificity N-glycosylases for the repair of oxidative DNA damage in the nucleus and mitochondria. Biochemistry 38:11298–11306

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr. A. Tzagoloff for kindly providing the mitochondrial mutant strains and Dr. M. Grey for constructing the q mutants. Research supported by Fundação de Amparo a Pesquisa do Estado da Bahia (FAPESB), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and GENOTOX. C. P. held a fellowship by FAPESB/CNPq (PRODOC Program). M.B. is Visiting Scientist supported by FAPESB. Part of the data is from the Master thesis of C.V. (PPGBCM-UFRGS).

Author information

Authors and Affiliations

  1. Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, Brasil

    C. Viau, M.C. Schmitt & J.A.P. Henriques

  2. Departamento de Biology, Universidade Estadual de Santa Cruz (UESC), Rodovia Ilhéus-Itabuna Km 16, CEP-45662-000, Ilhéus, Bahia, Brasil

    C. Pungartnik, T.S. Basso & M. Brendel

Authors
  1. C. Viau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Pungartnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M.C. Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T.S. Basso
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J.A.P. Henriques
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Brendel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Brendel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Viau, C., Pungartnik, C., Schmitt, M. et al. Sensitivity to Sn2+ of the Yeast Saccharomyces cerevisiae Depends on General Energy Metabolism, Metal Transport, Anti-Oxidative Defences, and DNA Repair. Biometals 19, 705–714 (2006). https://doi.org/10.1007/s10534-006-9007-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10534-006-9007-1

Keywords

Search

Navigation