title: Aneuploidy shortens replicative lifespan in Saccharomyces cerevisiae.
abstract: Aneuploidy and aging are correlated; however, a causal link between these two phenomena has remained elusive. Here, we show that yeast disomic for a single native yeast chromosome generally have a decreased replicative lifespan. In addition, the extent of this lifespan deficit correlates with the size of the extra chromosome. We identified a mutation in BUL1 that rescues both the lifespan deficit and a protein trafficking defect in yeast disomic for chromosome 5. Bul1 is an E4 ubiquitin ligase adaptor involved in a protein quality control pathway that targets membrane proteins for endocytosis and destruction in the lysosomal vacuole, thereby maintaining protein homeostasis. Concurrent suppression of the aging and trafficking phenotypes suggests that disrupted membrane protein homeostasis in aneuploid yeast may contribute to their accelerated aging. The data reported here demonstrate that aneuploidy can impair protein homeostasis, shorten lifespan, and may contribute to age-associated phenotypes.
authors.affiliation: Department of Genome Sciences, University of Washington, Foege Building, Room S403B, 3720 15th Ave NE, Box 355065, Seattle, WA, 98195-5065, USA.
authors.forename: Anna B
authors.initials: AB
authors.lastname: Sunshine
authors.affiliation: Department of Genome Sciences, University of Washington, Foege Building, Room S403B, 3720 15th Ave NE, Box 355065, Seattle, WA, 98195-5065, USA.
authors.forename: Giang T
authors.initials: GT
authors.lastname: Ong
authors.affiliation: Departments of Biochemistry and Physiology and Biophysics, University of Washington, Room HSB J-355, 1705 NE Pacific St, UW box 357350, Seattle, WA, 98195-7350, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Nickerson
authors.affiliation: Department of Pathology, University of Washington, Room HSB D-514, 1705 NE Pacific St, Box 357470, Seattle, WA, 98195-7470, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Carr
authors.affiliation: Department of Pathology, University of Washington, Room HSB D-514, 1705 NE Pacific St, Box 357470, Seattle, WA, 98195-7470, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Murakami
authors.affiliation: Department of Pathology, University of Washington, Room HSB D-514, 1705 NE Pacific St, Box 357470, Seattle, WA, 98195-7470, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Wasko
authors.affiliation: Department of Pathology, University of Washington, Room HSB D-514, 1705 NE Pacific St, Box 357470, Seattle, WA, 98195-7470, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Shemorry
authors.affiliation: Departments of Biochemistry and Physiology and Biophysics, University of Washington, Room HSB J-355, 1705 NE Pacific St, UW box 357350, Seattle, WA, 98195-7350, USA.
authors.forename: Alexey J
authors.initials: AJ
authors.lastname: Merz
authors.affiliation: Department of Pathology, University of Washington, Room HSB D-514, 1705 NE Pacific St, Box 357470, Seattle, WA, 98195-7470, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Kaeberlein
authors.affiliation: Department of Genome Sciences, University of Washington, Foege Building, Room S403B, 3720 15th Ave NE, Box 355065, Seattle, WA, 98195-5065, USA.
authors.forename: Maitreya J
authors.initials: MJ
authors.lastname: Dunham
mesh_terms: D000782:Aneuploidy; D021381:Protein Transport; D012307:Risk Factors; D012441:Saccharomyces cerevisiae / Q000235:genetics*
keywords: BUL1; aging; aneuploidy; protein trafficking; replicative lifespan