Plasmid Accumulation Reduces Life Span in Saccharomyces cerevisiae
Open Access
- 1 October 2003
- journal article
- Published by Elsevier BV
- Vol. 278 (43), 41607-41617
- https://doi.org/10.1074/jbc.m307025200
Abstract
Aging in the yeast Saccharomyces cerevisiae is under the control of multiple pathways. The production and accumulation of extrachromosomal rDNA circles (ERCs) is one pathway that has been proposed to bring about aging in yeast. To test this proposal, we have developed a plasmid-based model system to study the role of DNA episomes in reduction of yeast life span. Recombinant plasmids containing different replication origins, cis-acting partitioning elements, and selectable marker genes were constructed and analyzed for their effects on yeast replicative life span. Plasmids containing the ARS1 replication origin reduce life span to the greatest extent of the plasmids analyzed. This reduction in life span is partially suppressed by a CEN4 centromeric element on ARS1 plasmids. Plasmids containing a replication origin from the endogenous yeast 2 μ circle also reduce life span, but to a lesser extent than ARS1 plasmids. Consistent with this, ARS1 and 2 μ origin plasmids accumulate in ∼7-generation-old cells, but ARS1/CEN4 plasmids do not. Importantly, ARS1 plasmids accumulate to higher levels in old cells than 2 μ origin plasmids, suggesting a correlation between plasmid accumulation and life span reduction. Reduction in life span is neither an indirect effect of increased ERC levels nor the result of stochastic cessation of growth. The presence of a fully functional 9.1-kb rDNA repeat on plasmids is not required for, and does not augment, reduction in life span. These findings support the view that accumulation of DNA episomes, including episomes such as ERCs, cause cell senescence in yeast.Keywords
This publication has 46 references indexed in Scilit:
- A novel mitochondrial protein, Tar1p, is encoded on the antisense strand of the nuclear 25S rDNAGenes & Development, 2002
- Growing Old: Metabolic Control and Yeast AgingAnnual Review of Microbiology, 2002
- Mutations in DNA Replication Genes Reduce Yeast Life SpanMolecular and Cellular Biology, 2002
- hpr1Δ Affects Ribosomal DNA Recombination and Cell Life Span in Saccharomyces cerevisiaeMolecular and Cellular Biology, 2002
- Getting started with yeastMethods in enzymology, 2002
- Metabolic control and ageingTrends in Genetics, 2000
- A yeast gene product, Fob1 protein, required for both replication fork blocking and recombinational hotspot activitiesGenes to Cells, 1996
- The arrest of replication forks in the rDNA of yeast occurs independently of transcriptionCell, 1992
- Multifunctional yeast high-copy-number shuttle vectorsGene, 1992
- Clonal lethality caused by the yeast plasmid 2μ DNACell, 1982