title: Sir2-dependent asymmetric segregation of damaged proteins in ubp10 null mutants is independent of genomic silencing.
abstract: Carbonylation of proteins is an irreversible oxidative damage that increases during both chronological and replicative yeast aging. In the latter, a spatial protein quality control system that relies on Sir2 is responsible for the asymmetrical damage segregation in the mother cells. Proper localization of Sir2 on chromatin depends on the deubiquitinating enzyme Ubp10, whose loss of function deeply affects the recombination and gene-silencing activities specific to Sir2. Here, we have analyzed the effects of SIR2 and UBP10 inactivations on carbonylated protein patterns obtained in two aging models such as stationary phase cells and size-selected old mother ones. In line with the endogenous situation of higher oxidative stress resulting from UBP10 inactivation, an increase of protein carbonylation has been found in the ubp10Delta stationary phase cells compared with sir2Delta ones. Moreover, Calorie Restriction had a salutary effect for both mutants by reducing carbonylated proteins accumulation. Remarkably, in the replicative aging model, whereas SIR2 inactivation resulted in a failure to establish damage asymmetry, the Sir2-dependent damage inheritance is maintained in the ubp10Delta mutant which copes with the increased oxidative damage by retaining it in the mother cells. This indicates that both Ubp10 and a correct association of Sir2 with the silenced chromatin are not necessary in such a process but also suggests that additional Sir2 activities on non-chromatin substrates are involved in the establishment of damage asymmetry.
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, 20126 Milano, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Orlandi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bettiga
authors.forename: Lilia
authors.initials: L
authors.lastname: Alberghina
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyström
authors.forename: Marina
authors.initials: M
authors.lastname: Vai
mesh_terms: D016922:Cellular Senescence; D002843:Chromatin / Q000235:genetics; D004261:DNA Replication; D004271:DNA, Fungal; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D016681:Genome, Fungal; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / 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*; D025801:Ubiquitin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D004271:DNA, Fungal; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D025801:Ubiquitin; C403282:UBP10 protein, S cerevisiae; D043222:Ubiquitin Thiolesterase; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2