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.
Samanfar, B. (Bahram), Omidi, K. (Katayoun), Hooshyar, M. (Mohsen), Laliberte, B. (Ben), Alamgir, M. (Md), Seal, A.J. (Andrew J.), … Golshani, A. (Ardeshir). (2013). Large-scale investigation of oxygen response mutants in Saccharomyces cerevisiae. Molecular BioSystems, 9(6), 1351–1359. doi:10.1039/c3mb25516f