Regulatory kinase genetic interaction profiles differ between environmental conditions and cellular states Siyu Sun 10.6084/m9.figshare.12149469.v1 https://tagc2020.figshare.com/articles/poster/Regulatory_kinase_genetic_interaction_profiles_differ_between_environmental_conditions_and_cellular_states/12149469 <p><b>Cell growth and quiescence in eukaryotic cells is controlled by an evolutionarily conserved network of signaling pathways. Signal transduction networks operate to modulate a wide range of cellular processes and physiological properties when cells exit proliferative growth and initiate a quiescent state. How signaling networks function to respond to diverse signals that result in cell cycle exit and establishment of a quiescent state is poorly understood. Here, we studied the function of signaling pathways in quiescent cells using global genetic interaction mapping in the model eukaryotic cell, <i>Saccharomyces cerevisiae</i> (budding yeast). We performed pooled analysis of genotypes using molecular barcode sequencing (Bar-seq) to test the role of ~4,000 gene deletion mutants and ~12,000 pairwise interactions between all non-essential genes and the protein kinase genes <i>TOR1</i>, <i>RIM15</i>, <i>PHO85</i> in three different nutrient-restricted conditions in both proliferative and quiescent cells. We detect up to ten-fold more genetic interactions in quiescent cells compared to proliferative cells. We find that both individual gene effects and genetic interaction profiles vary depending on the specific pro-quiescence signal. The master regulator of quiescence, <i>RIM15</i> shows distinct genetic interaction profiles in response to different starvation signals. However, vacuole-related functions show consistent genetic interactions with <i>RIM15</i> in response to different starvation signals suggesting that <i>RIM15</i> integrates diverse signals to maintain protein homeostasis in quiescent cells. Our study expands genome-wide genetic interaction profiling to additional conditions, and phenotypes, and highlights the conditional dependence of epistasis.</b></p> 2020-04-20 22:39:55 Genetic interaction studies signaling kinases Nutrient starvation Quiescence Chronological aging Quantitative Genetics (incl. Disease and Trait Mapping Genetics)