Project description:Contains gene expression profiles of yeast single and double deletion mutants of gene-specific transcription factors. Genetic interactions were studied by comparing gene expression changes of double mutants with gene expression changes in the respective single mutants. Pairs of gene-specific transcription factors were chosen based on previous evidence for epistasis, including synthetic genetic interactions as well as common DNA binding.
Project description:Contains gene expression profiles of yeast single and double deletion mutants of gene-specific transcription factors. Genetic interactions were studied by comparing gene expression changes of double mutants with gene expression changes in the respective single mutants. Pairs of gene-specific transcription factors were chosen based on previous evidence for epistasis, including synthetic genetic interactions as well as common DNA binding.
Project description:Transcription profiling by array of yeast gcn2, gcn4 and gln3 deletion mutants treated with rapamycin or 3-amino-1,2,4-triazole (3-AT)
Project description:Sit4 is a PP2A-like Ser/Thr protein phosphatase implicated in the regulation of cellular processes important for cell survival during aging. We have previously shown that SIT4 deletion promotes vacuolar acidification, mitochondrial derepression and oxidative stress resistance, increasing yeast chronological lifespan. In this study, we performed a proteomic analysis of isolated vacuoles and yeast genetic interaction analysis to unravel how Sit4 influences vacuolar and mitochondrial function. By employing high-resolution mass spectrometry, we show that sit4Δ vacuolar membranes were enriched in Vps27 and Hse1, two proteins that are part of the endosomal sorting complex required for transport-0 complex. In addition, SIT4 exhibited a negative genetic interaction with VSP27, as sit4∆vps27∆ double mutants had a shortened lifespan compared to sit4∆ and vps27∆ single mutants. Our results also show that Vps27 did not increase sit4∆ lifespan by improving protein trafficking or vacuolar sorting pathways. However, Vps27 was critical for iron homeostasis and mitochondrial function in sit4∆ cells, as sit4∆vps27∆ double mutants exhibited high iron levels, impaired mitochondrial respiration and mitochondrial DNA (mtDNA) depletion. These findings show for the first-time a cross-talk between Sit4 and Vps27, providing new insights into the mechanisms governing chronological lifespan.
