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 extrachromosomal ribosomal DNA circles (ERCs). Introduction of an ERC into young mother cells shortens life span and accelerates the onset of age-associated sterility. It is important to understand the process by which ERCs are generated. Here, we demonstrate that homologous recombination is necessary for ERC formation. rad52 mutant cells, defective in DNA repair through homologous recombination, do not accumulate ERCs with age, and mutations in other genes of the RAD52 class have varying effects on ERC formation. rad52 mutation leads to a progressive delocalization of Sir3p from telomeres to other nuclear sites with age and, surprisingly, shortens life span. We speculate that 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-type cells.
Park
P U
PU
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Defossez
P A
PA
Guarente
L
L
D016922:Cellular Senescence / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004270:DNA, Circular / Q000235:genetics*; D004275:DNA, Ribosomal / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004843:Epistasis, Genetic; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005656:Fungal Proteins / Q000235:genetics; D005838:Genotype; D007246:Infertility / Q000235:genetics; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D051721:Rad52 DNA Repair and Recombination Protein; D011995:Recombination, Genetic / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D016615:Telomere / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
D004270:DNA, Circular; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; C084122:SIR3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015534:Trans-Activators