Open AccessRibosomal DNA and cellular senescence: new evidence supporting the connection between r DNA and aging
Author(s) -
Ganley Austen R. D.,
Kobayashi Takehiko
Publication year - 2014
Publication title -
fems yeast research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.991
H-Index - 92
eISSN - 1567-1364
pISSN - 1567-1356
DOI - 10.1111/1567-1364.12133
Subject(s) - biology , genome instability , ribosomal dna , genetics , saccharomyces cerevisiae , senescence , chromatin , dna repair , model organism , gene , computational biology , dna damage , dna , phylogenetics
The yeast S accharomyces cerevisiae is a powerful model system to understand the molecular basis of aging. It has been known for over 50 years that yeast cells have a finite replicative capacity and develop an aging phenotype, and much recent research has focused on the molecular changes that underlie this replicative senescence. A common thread in many yeast replicative aging studies is the involvement of the ribosomal DNA gene repeats (r DNA ), beginning with the discovery that the r DNA silencing gene, SIR2 , regulates life span. In 2008, a novel aging hypothesis, termed the r DNA theory of aging, was presented where the high level of genomic instability at the r DNA repeats was proposed to dominate global genome stability and determine the life span. Here, we review the r DNA theory of aging and discuss a number of recent studies that provide important new data on the roles of the r DNA in yeast replicative aging. Based on these recent results, we propose an integrative model of the r DNA theory of aging that encompasses genomic instability, chromatin relocalization following DNA repair, and replication stress in a self‐reinforcing cyclical pathway that is primarily manifested at the r DNA repeats and results in the aging phenotype.