Smc5/6 in the rDNA modulates lifespan independently of Fob1​

Aging Cell. 2021 Jun;20(6):e13373. doi: 10.1111/acel.13373. Epub 2021 May 12.

Abstract

The ribosomal DNA (rDNA) in Saccharomyces cerevisiae is in one tandem repeat array on Chromosome XII. Two regions within each repetitive element, called intergenic spacer 1 (IGS1) and IGS2, are important for organizing the rDNA within the nucleolus. The Smc5/6 complex localizes to IGS1 and IGS2. We show that Smc5/6 has a function in the rDNA beyond its role in homologous recombination (HR) at the replication fork barrier (RFB) located in IGS1. Fob1 is required for optimal binding of Smc5/6 at IGS1 whereas the canonical silencing factor Sir2 is required for its optimal binding at IGS2, independently of Fob1. Through interdependent interactions, Smc5/6 stabilizes Sir2 and Cohibin at both IGS and its recovery at IGS2 is important for nucleolar compaction and transcriptional silencing, which in turn supports rDNA stability and lifespan.

Keywords: Fob1; Smc5/6; nucleolar morphology; nucleolus; rDNA; replicative lifespan; silencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism*
  • DNA, Ribosomal / genetics*
  • DNA-Binding Proteins / metabolism*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • DNA, Ribosomal
  • DNA-Binding Proteins
  • FOB1 protein, S cerevisiae
  • SMC5 protein, S cerevisiae
  • SMC6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins