title: Aggregation of the Whi3 protein, not loss of heterochromatin, causes sterility in old yeast cells.
abstract: In yeast, heterochromatin silencing is reported to decline in aging mother cells, causing sterility in old cells. This process is thought to reflect a decrease in the activity of the NAD+(oxidized nicotinamide adenine dinucleotide)-dependent deacetylase Sir2. We tested whether Sir2 becomes nonfunctional gradually or precipitously during aging. Unexpectedly, silencing of the heterochromaticHMLandHMRloci was not lost during aging. Old cells could initiate a mating response; however, they were less sensitive to mating pheromone than were young cells because of age-dependent aggregation of Whi3, an RNA-binding protein controlling S-phase entry. Removing the polyglutamine domain of Whi3 restored the pheromone sensitivity of old cells. We propose that aging phenotypes previously attributed to loss of heterochromatin silencing are instead caused by aggregation of the Whi3 cell cycle regulator.
authors.affiliation: Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA 94720, USA.
authors.forename: Gavin
authors.identifier: 0000-0003-0490-7438
authors.initials: G
authors.lastname: Schlissel
authors.affiliation: Institute of Biochemistry, ETH Zürich, Zürich, Switzerland.
authors.forename: Marek K
authors.identifier: 0000-0002-9076-8704
authors.initials: MK
authors.lastname: Krzyzanowski
authors.affiliation: Institute of Biochemistry, ETH Zürich, Zürich, Switzerland.|King's College London, London, UK.
authors.forename: Fabrice
authors.identifier: 0000-0001-5159-1507
authors.initials: F
authors.lastname: Caudron
authors.affiliation: Institute of Biochemistry, ETH Zürich, Zürich, Switzerland. yves.barral@bc.biol.ethz.ch jrine@berkeley.edu.
authors.forename: Yves
authors.identifier: 0000-0002-0989-3373
authors.initials: Y
authors.lastname: Barral
authors.affiliation: Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA 94720, USA. yves.barral@bc.biol.ethz.ch jrine@berkeley.edu.
authors.forename: Jasper
authors.identifier: 0000-0003-2297-9814
authors.initials: J
authors.lastname: Rine
mesh_terms: D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D049770:Genes, Mating Type, Fungal; D006570:Heterochromatin / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000502:physiology; D066329:Protein Aggregates; D000072417:Protein Domains / Q000235:genetics / Q000502:physiology; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D059807:S Phase Cell Cycle Checkpoints; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism; D056565:Sirtuin 2 / Q000378:metabolism
chemical_list: D006570:Heterochromatin; D010455:Peptides; D066329:Protein Aggregates; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C440012:Whi3 protein, S cerevisiae; C097188:polyglutamine; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2