Rapamycin increases rDNA stability by enhancing association of Sir2 with rDNA in Saccharomyces cerevisiae
Open Access
- 14 October 2010
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 39 (4), 1336-1350
- https://doi.org/10.1093/nar/gkq895
Abstract
The target of rapamycin (TOR) kinase is an evolutionarily conserved key regulator of eukaryotic cell growth and proliferation. Recently, it has been reported that inhibition of TOR signaling pathway can delay aging and extend lifespan in several eukaryotic organisms, but how lifespan extension is mediated by inhibition of TOR signaling is poorly understood. Here we report that rapamycin treatment and nitrogen starvation, both of which cause inactivation of TOR complex 1 (TORC1), lead to enhanced association of Sir2 with ribosomal DNA (rDNA) in Saccharomyces cerevisiae. TORC1 inhibition increases transcriptional silencing of RNA polymerase II-transcribed gene integrated at the rDNA locus and reduces homologous recombination between rDNA repeats that causes formation of toxic extrachromosomal rDNA circles. In addition, TORC1 inhibition induces deacetylation of histones at rDNA. We also found that Pnc1 and Net1 are required for enhancement of association of Sir2 with rDNA under TORC1 inhibition. Taken together, our findings suggest that inhibition of TORC1 signaling stabilizes the rDNA locus by enhancing association of Sir2 with rDNA, thereby leading to extension of replicative lifespan in S. cerevisiae.Keywords
This publication has 72 references indexed in Scilit:
- Rapamycin fed late in life extends lifespan in genetically heterogeneous miceNature, 2009
- Histone H4 lysine 16 acetylation regulates cellular lifespanNature, 2009
- Yeast Life Span Extension by Depletion of 60S Ribosomal Subunits Is Mediated by Gcn4Cell, 2008
- eIF4E function in somatic cells modulates ageing in Caenorhabditis elegansNature, 2007
- Sirtuin activators mimic caloric restriction and delay ageing in metazoansNature, 2004
- Influence of TOR kinase on lifespan in C. elegansNature, 2003
- Global analysis of protein localization in budding yeastNature, 2003
- Getting started with yeastMethods in enzymology, 2002
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Studies on the transformation of intact yeast cells by the LiAc/SS‐DNA/PEG procedureYeast, 1995