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Large-scale investigation of oxygen response mutants in Saccharomyces cerevisiae.

A genome-wide screen of a yeast non-essential gene-deletion library was used to identify sick phenotypes due to oxygen deprivation. The screen provided a manageable list of 384 potentially novel as well as known oxygen responding (anoxia-survival) genes. The gene-deletion mutants were further assayed for sensitivity to ferrozine and cobalt to obtain a subset of 34 oxygen-responsive candidate genes including the known hypoxic gene activator, MGA2. With each mutant in this subset a plasmid based β-galactosidase assay was performed using the anoxic-inducible promoter from OLE1 gene, and 17 gene deletions were identified that inhibit induction under anaerobic conditions. Genetic interaction analysis for one of these mutants, the RNase-encoding POP2 gene, revealed synthetic sick interactions with a number of genes involved in oxygen sensing and response. Knockdown experiments for CNOT8, human homolog of POP2, reduced cell survival under low oxygen condition suggesting a similar function in human cells.

Pubmed ID: 23467670

Authors

  • Samanfar B
  • Omidi K
  • Hooshyar M
  • Laliberte B
  • Alamgir M
  • Seal AJ
  • Ahmed-Muhsin E
  • Viteri DF
  • Said K
  • Chalabian F
  • Golshani A
  • Wainer G
  • Burnside D
  • Shostak K
  • Bugno M
  • Willmore WG
  • Smith ML
  • Golshani A

Journal

Molecular bioSystems

Publication Data

June 8, 2013

Associated Grants

None

Mesh Terms

  • Cell Hypoxia
  • Cell Line
  • Cell Survival
  • Cobalt
  • Fatty Acid Desaturases
  • Ferrozine
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal
  • Humans
  • Iron Chelating Agents
  • Membrane Proteins
  • Oxygen
  • Promoter Regions, Genetic
  • Ribonucleases
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Trace Elements
  • Transcription Factors
  • Transcriptional Activation
  • beta-Galactosidase