Fraction of cells that died within 60 min of exposure to antifungal drug fluphenazine

Range cells with low Heat Shock Protein 12 (HSP12) 99%: cells with high HSP12 25% %
Organism Budding yeast Saccharomyces cerevisiae
Reference Gilad Yaakov, David Lerner, Kajetan Bentele, Joseph Steinberger and Naama Barkai, Coupling phenotypic persistence to DNA damage increases genetic diversity in severe stress, Nature Ecology & Evolution 1, Article number: 0016 (2017) pdf link doi:10.1038/s41559-016-0016 p.4 left column
Method Abstract: "[Investigators] report that spontaneous DNA damage triggers persistence in Saccharomyces cerevisiae by activating the general stress response, providing protection against a range of harsh stress and drug environments."
Comments P.2 right column bottom paragraph to p.4 right column: "Consistent with the idea that DNA damage triggers persistence, [investigators] find an increased fraction of persisters in strains showing elevated mutation rates, as indicated by higher fractions of extreme Hsp12-expressing cells with increased stress survival (Supplementary Fig. 4). To verify directly that DNA damage triggers persistence, [they] induced DSBs [double-strand breaks] by expressing a GAL1-inducible HO (homothallic switching) endonuclease in cells with a single HO cleavage site. Inducing HO led to the appearance of Rad52-GFP foci, followed by a delayed (~2 h) induction of Hsp12-mCherry (Fig. 2f,g and Supplementary Fig. 5). Subjecting cells to fluphenazine confirmed that cells became persisters (Fig. 2h and Supplementary Videos 5 and 6). While ~99% of cells with low Hsp12 died within 60 min of exposure, only 25% of high Hsp12 cells died at that time, with survivors losing viability at a significantly lower rate (Fig. 2i). Nearly all survivors had Rad52 foci (Fig. 2h). [They] conclude that a severe DNA damage, such as DSB, triggers persistence in budding yeast."
Entered by Uri M
ID 113261