Effects of mutations in DNA repair genes on formation of ribosomal DNA circles and life span in Saccharomyces cerevisiae

A cause of aging in Saccharomyces cerevisiae is the accumulation of extrach romosomal ribosomal DNA circles (ERCs). Introduction of an ERC into young m other cells shortens life span and accelerates the onset of age-associated sterility. It is important to understand the process by which ERCs are gene rated. Here, we demonstrate that homologous recombination is necessary for ERC formation. rad52 mutant cells, defective in DNA repair through homologo us recombination, do not accumulate ERCs with age, and mutations in other g enes of the RAD52 class have varying effects on ERC formation, rad52 mutati on leads to a progressive delocalization of Sir3p from telomeres to other n uclear sites with age and, surprisingly, shortens life span. We speculate t hat spontaneous DNA damage, perhaps double-strand breaks, causes lethality in mutants of the RAD52 class and may be an initial step of aging in wild-t ype cells.