BFR1, a multicopy suppressor of brefeldin A-induced lethality, is implicated in secretion and nuclear segregation in Saccharomyces cerevisiae.
Brefeldin A (BFA) blocks protein transport out of the Golgi apparatus and causes disassembly of this organelle in mammalian cells. The primary effect of BFA is the release of the non-clathrin coat from Golgi membranes and vesicles. We sought to elucidate the mechanism of BFA action using a genetic approach in Saccharomyces cerevisiae. When an erg6 S. cerevisiae strain is treated with BFA, cell growth is arrested, cells lose viability and secretory proteins are accumulated in the endoplasmic reticulum (ER) and early Golgi compartments. We demonstrate that the mutant sec21 (defective in the S. cerevisiae homolog of gamma-COP, a non-clathrin coat protein) is supersensitive to BFA. Hence BFA probably affects the same processes in S. cerevisiae as in mammalian cells. We used a multicopy genomic DNA library to search for multicopy suppressors of BFA-induced lethality. We identified one such gene, BFR1, that, in addition, partially suppresses the growth and secretion defects of the ER-to-Golgi secretion mutant sec17. A bfr1-delta 1::URA3 deletion strain is viable, but has defects in cell morphology and nuclear segregation, and the mutation accentuates the growth and secretion defects of a sec21 mutant.
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Département de Biologie Cellulaire et Moléculaire, Centre d'Etudes de Saclay, Gif-sur-Yvette, France.
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D020126:Brefeldin A; D002467:Cell Nucleus / Q000502:physiology*; D003001:Cloning, Molecular; D003517:Cyclopentanes / Q000633:toxicity*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D005800:Genes, Fungal; D005838:Genotype; D006056:Golgi Apparatus / Q000378:metabolism; D008322:Mammals; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic
C089100:BFR1 protein, S cerevisiae; D003517:Cyclopentanes; D005656:Fungal Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D020126:Brefeldin A