Loss of tRNA methyltransferase 9 and DNA damage response genes in yeast confers sensitivity to aminoglycosides.

tRNA methyltransferase 9 (Trm9)-catalysed tRNA modifications have been shown to translationally enhance the DNA damage response (DDR). Here, we show that Saccharomyces cerevisiae trm9Δ, distinct DNA repair and spindle assembly checkpoint (SAC) mutants are differentially sensitive to the aminoglycosides tobramycin, gentamicin and amikacin, indicating DDR and SAC activation might rely on translation fidelity, under aminoglycoside stress. Further, we report that the DNA damage induced by aminoglycosides in the base excision repair mutants ogg1Δ and apn1Δ is mediated by reactive oxygen species, which induce the DNA adduct 8-hydroxy deoxyguanosine. Finally, the synergistic effect of tobramycin and the DNA-damaging agent bleomycin to sensitize trm9Δ and the DDR mutants mlh1Δ, rad51Δ, mre11Δ and sgs1Δ at significantly lower concentrations compared with wild-type suggests that cells with tRNA modification dysregulation and DNA repair gene defects can be selectively sensitized using a combination of translation inhibitors and DNA-damaging agents.

Magnolol protects Saccharomyces cerevisiae antioxidant-deficient mutants from oxidative stress and extends yeast chronological life span.

We investigated the protective effect of a natural polyphenol, magnolol, on Saccharomyces cerevisiae cells under oxidative stress, and during aging. Our results showed the sensitivity of S. cerevisiae antioxidant gene deficient mutants (sod1∆, sod2∆, cta1∆, ctt1∆, gtt2∆ and tsa1∆) against hydrogen peroxide (H2O2) and menadione stress was rescued by magnolol as demonstrated in spot and colony forming unit counts. Yeast cells pretreated with magnolol showed decreased intracellular oxidation, lipid peroxidation and an increased level of reduced glutathione. Further, SOD1, CTA1 and GTT2 gene expression was examined by reverse transcription-polymerase chain reaction, and was found that magnolol significantly attenuated the upregulation of SOD1 and CTA1 genes under oxidative stress. Finally, longevity of the wild type and sod1 mutant cells were extended by magnolol, and also enhance stress resistance against oxidant stress during chronological aging.

Astaxanthin enhances the longevity of Saccharomyces cerevisiae by decreasing oxidative stress and apoptosis.

The budding yeast, Saccharomyces cerevisiae, is an efficient model for studying oxidative stress, programmed cell death and aging. The present study was carried out to investigate antioxidant, the anti-apoptotic and anti-aging activity of a natural compound, astaxanthin, in S. cerevisiae model. The survivability of yeast antioxidant-deficient strains (sod1Δ, sod2Δ, cta1Δ, ctt1Δ and tsa1Δ) increased by 20%-40% when cells were pre-treated with astaxanthin, compared to hydrogen peroxide alone, as demonstrated in spot and colony forming unit assays. Reduced reactive oxygen species (ROS) levels, increased glutathione, decreased lipid peroxidation and induced superoxide dismutase activity in astaxanthin-treated cells indicate that astaxanthin protected the cells from oxidative-stress-induced cell death. In addition, astaxanthin protected anti-apoptotic-deficient strains (pep4Δ and fis1Δ) against acetic acid and hydrogen peroxide-induced cell death that suggests anti-apoptotic property of astaxanthin, and it was further confirmed by acridine orange/ethidium bromide, annexin V and 4',6-diamidino-2-phenylindole staining. The yeast chronological lifespan assay results showed that astaxanthin extends the lifespan of antioxidant-deficient strains by scavenging ROS, and anti-apoptotic-deficient mutants by protecting from apoptotic cell death compared to their respective untreated cells and wild type. Our results suggest that astaxanthin enhances the longevity of yeast S. cerevisiae by reducing oxidative stress and apoptosis.