Beyond ERCs: exploring catastrophic forms of rDNA instability in aging yeast

Area of Science:

• Cellular aging
• Genetics
• Molecular biology

Background:

• Identical conditions do not yield identical life spans in single-celled organisms.
• Understanding aging variability is key to fundamental aging research.
• Chromosome XII instability is implicated in yeast aging.

Purpose of the Study:

• Investigate chromosome XII instability as a source of life span variability in aging yeast (Saccharomyces cerevisiae).
• Quantify karyotype, DNA content, and aberrant DNA structures, including extrachromosomal rDNA circles (ERCs).
• Propose a model for the generation of unresolved rDNA structures.

Main Methods:

• Tracking aging mother cell populations.
• Quantifying karyotype and DNA content.
• Analyzing aberrant DNA structures and ERC production.
• Developing a recombination model (CICR).

Main Results:

• Massive amplification of rDNA observed, both as ERCs and unresolved structures.
• Unresolved structures could not be resolved on CHEF gels.
• Proposed Catastrophic IntraChromosomal Recombination (CICR) model explains formation of these structures.
• CICR involves recombination between repeats of different replication statuses, leaving single replication forks.

Conclusions:

• Instability within the ribosomal DNA (rDNA) can generate toxic recombination products.
• These products contribute to life span variability in isogenic yeast populations.
• The CICR model provides a mechanism for rDNA instability during aging.