Authors: Defossez PA; Prusty R; Kaeberlein M; Lin SJ; Ferrigno P; Silver PA; Keil RL; Guarente L
Abstract: A cause of aging in yeast is the accumulation of circular species of ribosomal DNA (rDNA) arising from the 100-200 tandemly repeated copies in the genome. We show here that mutation of the FOB1 gene slows the generation of these circles and thus extends life span. Fob1p is known to create a unidirectional block to replication forks in the rDNA. We show that Fob1p is a nucleolar protein, suggesting a direct involvement in the replication fork block. We propose that this block can trigger aging by causing chromosomal breaks, the repair of which results in the generation of rDNA circles. These findings may provide a novel link between metabolic rate and aging in yeast and, perhaps, higher organisms.
Keywords: DNA Repair/genetics; DNA Replication/*genetics; DNA, Circular/genetics; DNA, Ribosomal/genetics; *DNA-Binding Proteins; Fluorescent Antibody Technique; Fungal Proteins/*genetics; Gene Deletion; Green Fluorescent Proteins; Luminescent Proteins; Nuclear Proteins/genetics; Repetitive Sequences, Nucleic Acid; Saccharomyces cerevisiae/*genetics; *Saccharomyces cerevisiae Proteins|
Journal: Molecular cell Volume: 3 Issue: 4 Pages: 447-55 Date: May 7, 1999 PMID: 10230397 |
Defossez PA, Prusty R, Kaeberlein M, Lin SJ, Ferrigno P, Silver PA, Keil RL, Guarente L (1999) Elimination of replication block protein Fob1 extends the life span of yeast mother cells. Molecular cell 3: 447-55.
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