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PLoS One. 2017 May 17;12(5):e0176085. doi: 10.1371/journal.pone.0176085. eCollection 2017.

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

Choi J1,2,3, Rajagopal A1,3,4, Xu YF5,6, Rabinowitz JD5,6, O'Shea EK1,2,3,4.

Author information

1
Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, Massachusetts, United States of America.
2
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America.
3
Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, United States of America.
4
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, United States of America.
5
Department of Chemistry, Princeton University, Princeton, New Jersey, United States of America.
6
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.

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.

PMID:
28520786
PMCID:
PMC5435139
DOI:
10.1371/journal.pone.0176085
[Indexed for MEDLINE]
Free PMC Article

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