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Title: A systematic genetic screen for genes involved in sensing inorganic phosphate availability in Saccharomyces cerevisiae

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 P i. P i-limitation induces upregulation of inositol heptakisphosphate (IP 7) 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. Moreover, we showed that even in the absence of VIP1, the PHO pathway can be activated under prolonged periods of P i starvation, suggesting complexity in the mechanisms by which the PHO pathway is regulated.
ORCiD logo [1] ;  [2] ;  [3] ;  [3] ;  [4] ;  [5]
  1. California Inst. of Technology (CalTech), Pasadena, CA (United States); Harvard Univ., Cambridge, MA (United States)
  2. Harris County Public Health, Houston, TX (United States); Harvard Univ., Cambridge, MA (United States)
  3. Princeton Univ., Princeton, NJ (United States)
  4. Howard Hughes Medical Inst., Chevy Chase, MD (United States); Harvard Univ., Cambridge, MA (United States)
  5. Texas A & M Univ., College Station, TX (United States)
Publication Date:
Grant/Contract Number:
Published Article
Journal Name:
Additional Journal Information:
Journal Volume: 12; Journal Issue: 5; Journal ID: ISSN 1932-6203
Public Library of Science
Research Org:
Princeton Univ., NJ (United States)
Sponsoring Org:
USDOE Office of Science (SC)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; adenine; metabolic pathways; epistasis; genetic screens; phenotypes; gene regulation; genomic signal processing; Saccharomyces cerevisiae
OSTI Identifier:
Alternate Identifier(s):
OSTI ID: 1389780