, Volume 19, Issue 6, pp 705-714
Date: 12 May 2006

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

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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.