Plasmid accumulation reduces life span in Saccharomyces cerevisiae

Area of Science:

• Cellular and Molecular Biology
• Yeast Genetics
• Aging Research

Background:

• Aging in Saccharomyces cerevisiae is influenced by multiple cellular pathways.
• Extrachachromosomal rDNA circles (ERCs) are a proposed mechanism driving yeast aging.
• Understanding the role of DNA episomes in lifespan reduction is crucial.

Purpose of the Study:

• To investigate the role of DNA episomes in reducing yeast replicative lifespan.
• To develop and utilize a plasmid-based model system for studying episome accumulation.
• To correlate specific plasmid features with lifespan reduction and accumulation levels.

Main Methods:

• Construction and analysis of recombinant plasmids with varying replication origins (ARS1, 2 mu) and partitioning elements (CEN4).
• Assessment of the impact of these plasmids on the replicative lifespan of yeast Saccharomyces cerevisiae.
• Quantification of plasmid accumulation in yeast cells across generations.

Main Results:

• Plasmids with the ARS1 replication origin most significantly reduced yeast lifespan.
• The CEN4 centromeric element partially suppressed lifespan reduction caused by ARS1 plasmids.
• ARS1 and 2 mu origin plasmids accumulated in older cells, with ARS1 showing higher accumulation and greater lifespan reduction.

Conclusions:

• Accumulation of DNA episomes, including ERCs, is a causative factor in yeast cell senescence.
• The degree of episome accumulation correlates with the extent of lifespan reduction.
• Specific replication origins influence both episome accumulation and lifespan reduction in yeast.