The SCR1 gene from Schwanniomyces occidentalis encodes a highly hydrophobic polypeptide, which confers ribosomal resistance to cycloheximide.
In Saccharomyces cerevisiae, the SCR1 gene from Schwanniomyces occidentalis is known to induce ribosomal resistance to cycloheximide (cyh). A 2.8 kb DNA fragment encoding this gene was sequenced. Its EMBL Accession No. is AJ419770. It disclosed a putative tRNA(Asn) (GUU) sequence located downstream of an open reading frame (ORF) of 1641 nucleotides. This ORF was shown to correspond to SCR1. It would encode a highly hydrophobic polypeptide (SCR1) with 12 transmembrane domains. SCR1 is highly similar to a variety of yeast proteins of the multidrug-resistance (MDR) family. However, SCR1 only conferred resistance to cyh but not to benomyl or methotrexate. The cyh-resistance phenotype induced by SCR1 was confirmed in several S. cerevisiae strains that expressed this gene to reside at the ribosomal level. In contrast, a beta-galacosidase-tagged SCR1 was found to be integrated in the endoplasmic reticulum (ER). It is proposed that the ribosomes of yeast cells expressing SCR1 undergo a conformational change during their interaction with the ER, which lowers their affinity for cyh-binding. If so, these findings would disclose a novel ribosomal resistance mechanism.
Hoenicka
Janet
J
Centro de Biología Molecular, Universidad Autónoma de Madrid, Canto Blanco, 28049 Madrid, Spain.
Fernández Lobato
María
M
Marín
Dolores
D
Jiménez
Antonio
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003513:Cycloheximide / Q000494:pharmacology; D005800:Genes, Fungal; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012343:RNA, Transfer / Q000235:genetics; D012270:Ribosomes / Q000187:drug effects; D004718:Saccharomycetales / Q000187:drug effects / Q000235:genetics*; D016415:Sequence Alignment
D011500:Protein Synthesis Inhibitors; D012343:RNA, Transfer; D003513:Cycloheximide