부산대학교 도서관

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, Saccharomyces cerevisiae (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 TOR1,RIM15, and PHO85 in three different nutrient‐restricted conditions in both proliferative and quiescent cells. We detect up to 10‐fold more genetic interactions in quiescent cells than 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, RIM15, shows distinct genetic interaction profiles in response to different starvation signals. However, vacuole‐related functions show consistent genetic interactions with RIM15 in response to different starvation signals, suggesting that RIM15 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. Synopsis: A pooled analysis of genotypes using Bar‐seq shows that the genetic and functional requirements of proliferative and quiescent cells differ between conditions. Quantitative genetic interaction mapping reveals condition‐dependent genetic interaction profiles for the core regulatory kinases. Genetic interactions in thousands of mutants are studied using pooled assays and time series analyses using Bar‐seq, enabling efficient study of additional phenotypes such as survival of nutrient starvation.The genetic interactions of the signaling kinase genes TOR1, RIM15, PHO85 vary between different environmental conditions and cellular states.RIM15 interacts with similar functional classes of genes in different starvation conditions consistent with its role as a master regulator of quiescence.Unique and cohesive positive genetic interactions between RIM15 and Endoplasmic‐reticulum‐associated protein degradation (ERAD) genes point to a new functional relationship when responding to nitrogen starvation. [ABSTRACT FROM AUTHOR]