hpr1Δ Affects Ribosomal DNA Recombination and Cell Life Span in Saccharomyces cerevisiae

Abstract

Multiple genetic pathways have been shown to regulate life span and aging in the yeast Saccharomyces cerevisiae. Here we show that loss of a component of the RNA polymerase II complex, Hpr1p, results in a decreased life span. Although hpr1Δ mutants have an increased rate of recombination within the ribosomal DNA (rDNA) array, this is not accompanied by an increase in extrachromosomal rDNA circles (ERCs). Analyses of mutants that affect replication of the rDNA array and suppressors that reverse the phenotypes of the hpr1Δ mutant show that the reduced life span is associated with increased genomic instability but not with increased ERC formation. The hpr1Δ mutant acts in a pathway distinct from previously described mutants that reduce life span.

We thank L. Guarente for the yeast strain W303R and for the generous gift of the biotin magnetic beads. We thank E. Nudler for comments and critical reading of the manuscript.

This work was supported by grant GM30439 from the National Institutes of Health.