A systematic genetic screen for genes involved in sensing inorganic phosphate availability in Saccharomyces cerevisiae. Author Joonhyuk Choi, Abbhirami Rajagopal, Yi-Fan Xu, Joshua Rabinowitz, Erin O'Shea Publication Year 2017 Type Journal Article Abstract Saccharomyces cerevisiae responds to changes in extracellular inorganic phosphate (Pi) availability by regulating the activity of the phosphate-responsive (PHO) signaling pathway, enabling cells to maintain intracellular levels of the essential nutrient Pi. Pi-limitation induces upregulation of inositol heptakisphosphate (IP7) synthesized by the inositol hexakisphosphate kinase Vip1, triggering inhibition of the Pho80/Pho85 cyclin-cyclin dependent kinase (CDK) complex by the CDK inhibitor Pho81, which upregulates the PHO regulon through the CDK target and transcription factor Pho4. To identify genes that are involved in signaling upstream of the Pho80/Pho85/Pho81 complex and how they interact with each other to regulate the PHO pathway, we performed genome-wide screens with the synthetic genetic array method. We identified more than 300 mutants with defects in signaling upstream of the Pho80/Pho85/Pho81 complex, including AAH1, which encodes an adenine deaminase that negatively regulates the PHO pathway in a Vip1-dependent manner. Furthermore, we showed that even in the absence of VIP1, the PHO pathway can be activated under prolonged periods of Pi starvation, suggesting complexity in the mechanisms by which the PHO pathway is regulated. Keywords Gene Expression Regulation, Fungal, Saccharomyces cerevisiae, Phosphates, Saccharomyces cerevisiae Proteins, Genome, Fungal Journal PLoS One Volume 12 Issue 5 Pages e0176085 ISSN Number 1932-6203 DOI 10.1371/journal.pone.0176085 Alternate Journal PLoS ONE PMCID PMC5435139 PMID 28520786 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML