title: Perinuclear cohibin complexes maintain replicative life span via roles at distinct silent chromatin domains.
abstract: Heterochromatin, or silent chromatin, preferentially resides at the nuclear envelope. Telomeres and rDNA repeats are the two major perinuclear silent chromatin domains of Saccharomyces cerevisiae. The Cohibin protein complex maintains rDNA repeat stability in part through silent chromatin assembly and perinuclear rDNA anchoring. We report here a role for Cohibin at telomeres and show that functions of the complex at chromosome ends and rDNA maintain replicative life span. Cohibin binds LEM/SUN domain-containing nuclear envelope proteins and telomere-associated factors. Disruption of Cohibin or the envelope proteins abrogates telomere localization and silent chromatin assembly within subtelomeres. Loss of Cohibin limits Sir2 histone deacetylase localization to chromosome ends, disrupts subtelomeric DNA stability, and shortens life span even when rDNA repeats are stabilized. Restoring telomeric Sir2 concentration abolishes chromatin and life span defects linked to the loss of telomeric Cohibin. Our work uncovers roles for Cohibin complexes and reveals relationships between nuclear compartmentalization, chromosome stability, and aging.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
authors.forename: Janet N Y
authors.initials: JN
authors.lastname: Chan
authors.forename: Betty P K
authors.initials: BP
authors.lastname: Poon
authors.forename: Jayesh
authors.initials: J
authors.lastname: Salvi
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Olsen
authors.forename: Andrew
authors.initials: A
authors.lastname: Emili
authors.forename: Karim
authors.initials: K
authors.lastname: Mekhail
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006570:Heterochromatin / Q000235:genetics*; D008136:Longevity; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009685:Nuclear Envelope / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics*
chemical_list: C474335:CSM1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; C556514:Heh2 protein, S cerevisiae; D006570:Heterochromatin; C474336:LRS4 protein, S cerevisiae; D008565:Membrane Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C081647:high affinity DNA-binding factor, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2