The SAGA histone deubiquitinase module controls yeast replicative lifespan via Sir2 interaction.

Abstract

We have analyzed the yeast replicative lifespan of a large number of open reading frame (ORF) deletions. Here, we report that strains lacking genes SGF73, SGF11, and UBP8 encoding SAGA/SLIK complex histone deubiquitinase module (DUBm) components are exceptionally long lived. Strains lacking other SAGA/SALSA components, including the acetyltransferase encoded by GCN5, are not long lived; however, these genes are required for the lifespan extension observed in DUBm deletions. Moreover, the SIR2-encoded histone deacetylase is required, and we document both a genetic and physical interaction between DUBm and Sir2. A series of studies assessing Sir2-dependent functions lead us to propose that DUBm strains are exceptionally long lived because they promote multiple prolongevity events, including reduced rDNA recombination and altered silencing of telomere-proximal genes. Given that ataxin-7, the human Sgf73 ortholog, causes the neurodegenerative disease spinocerebellar ataxia type 7, our findings indicate that the genetic and epigenetic interactions between DUBm and SIR2 will be relevant to neurodegeneration and aging.

• Authors: Mark A McCormick, Amanda G Mason, Stephan J Guyenet, Weiwei Dang, Renee M Garza, Marc K Ting, Rick M Moller, Shelley L Berger, Matt Kaeberlein, Lorraine Pillus, Albert R La Spada, Brian K Kennedy
• Journal: Cell reports (Cell Rep) Vol. 8 Issue 2 Pg. 477-86 (Jul 24 2014) ISSN: 2211-1247 [Electronic] United States
• PMID: 25043177 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• SAGA complex, S cerevisiae
• Saccharomyces cerevisiae Proteins
• Silent Information Regulator Proteins, Saccharomyces cerevisiae
• Trans-Activators
• GCN5 protein, S cerevisiae
• Histone Acetyltransferases
• Sgf73 protein, S cerevisiae
• Endopeptidases
• UBP8 protein, S cerevisiae
• SIR2 protein, S cerevisiae
• Sirtuin 2

Topics

• Cell Proliferation
• DNA Replication
• Endopeptidases (genetics, metabolism)
• Histone Acetyltransferases (genetics, metabolism)
• Protein Binding
• Saccharomyces cerevisiae (genetics, metabolism, physiology)
• Saccharomyces cerevisiae Proteins (genetics, metabolism)
• Silent Information Regulator Proteins, Saccharomyces cerevisiae (genetics, metabolism)
• Sirtuin 2 (genetics, metabolism)
• Trans-Activators (genetics, metabolism)