title: The nuclear GTPase Gsp1p can affect proper telomeric function through the Sir4 protein in Saccharomyces cerevisiae.
abstract: The small Ras-like GTPase Ran/Gsp1p is a highly conserved nuclear protein required for the nucleocytoplasmic trafficking of macromolecules. Recent findings suggest that the Ran/Gsp1p pathway may have additional roles in several aspects of nuclear structure and function, including spindle assembly, nuclear envelope formation, nuclear pore complex assembly and RNA processing. Here, we provide evidence that Gsp1p can regulate telomeric function in Saccharomyces cerevisiae. We show that overexpression of PRP20, encoding the Gsp1p GDP/GTP nuclear exchange factor, specifically weakens telomeric silencing without detectably affecting nucleocytoplasmic transport. In addition to this silencing defect, we show that Rap1p and Sir3p delocalize from their normal telomeric foci. Interestingly, Gsp1p was found to interact genetically and physically with the telomeric component Sir4p. Taken together, these results suggest that the GSP1 pathway could regulate proper telomeric function in yeast through Sir4p.
authors.affiliation: Département de microbiologie et immunologie, Université de Montréal, C P 6128, succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Clément
authors.forename: Francis
authors.initials: F
authors.lastname: Deshaies
authors.forename: Louis
authors.initials: L
authors.lastname: de Repentigny
authors.forename: Pierre
authors.initials: P
authors.lastname: Belhumeur
mesh_terms: D047369:Chromatin Immunoprecipitation; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D000089804:Shelterin Complex; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C080324:GSP1 protein, S cerevisiae; D009687:Nuclear Proteins; C440829:RAP1 protein, S cerevisiae; C084122:SIR3 protein, S cerevisiae; C061573:SIR4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; D020558:GTP Phosphohydrolases; D020559:Monomeric GTP-Binding Proteins; D020931:ran GTP-Binding Protein