Smc5/6 in the rDNA modulates lifespan independently of Fob1
| Autor: | Troy A. A. Harkness, Jennifer A. Cobb, Sarah Moradi-Fard, Aditya Mojumdar, Megan Chan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Aging Saccharomyces cerevisiae Proteins Nucleolus Saccharomyces cerevisiae rDNA Cell Cycle Proteins nucleolar morphology Biology DNA Ribosomal 03 medical and health sciences 0302 clinical medicine Tandem repeat Animals Gene silencing nucleolus replicative lifespan Ribosomal DNA Original Paper Chromosome Original Articles Cell Biology biology.organism_classification Cell biology DNA-Binding Proteins Fob1 030104 developmental biology silencing Smc5/6 Homologous recombination 030217 neurology & neurosurgery Function (biology) |
| Zdroj: | Aging Cell |
| ISSN: | 1474-9726 1474-9718 |
| DOI: | 10.1111/acel.13373 |
| Popis: | 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. Smc5/6 is important for transcriptional silencing in the rDNA. rDNA compaction requires Smc5/6 localization to IGS regions. Transcriptional silencing of ncRNA at IGS1 and IGS2 is differentially regulated. Smc5/6 has a role in rDNA maintenance independent of HR processing at the RFB. Fob1‐independent disruption of Smc5/6 leads to lifespan reduction. |
| Databáze: | OpenAIRE |
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