ABSTRACT
Genes that are essential for growth in yeast were screened to identify those involved in arsenite sensitivity. We found that the knockdown of YPT1, ERG8, or RKI1 enhanced arsenite sensitivity in yeast.
Subject(s)
Arsenites/toxicity , Genes, Fungal/genetics , Saccharomyces cerevisiae/growth & development , Saccharomyces cerevisiae/genetics , Aldose-Ketose Isomerases/genetics , Gene Expression Regulation, Fungal , Gene Knockdown Techniques , Genes, Essential/genetics , Phosphotransferases (Phosphate Group Acceptor)/genetics , Real-Time Polymerase Chain Reaction , Saccharomyces cerevisiae Proteins/genetics , rab GTP-Binding Proteins/geneticsABSTRACT
To elucidate the role of ribosomes in the manifestation of adriamycin toxicity, ribosome-binding proteins involved in adriamycin sensitivity were identified using budding yeast as a eukaryotic model. This revealed that adriamycin toxicity was enhanced byloss of the Egd1 or Egd2 subunits of the nascent polypeptide-associated complex(NAC). NAC is a heterodimer consisting of alpha (Egd2) and beta (Egd1 or Btt1)subunits, and is known to be involved in the translocation of nascent polypeptides into mitochondria or endoplasmic reticulum and in transcriptional activation in the nucleus. Because the loss of the Btt1 subunit had no effect on adriamycin sensitivity, the NAC conformation responsible for resistance to adriamycin appears to be the Egd1/Egd2 complex. We propose that functional NACin the ribosome is involved in resistance to adriamycin toxicity.
