Elimination of replication block protein Fob1 extends the life span of yeast mother cells

A cause of aging in yeast is the accumulation of circular species of riboso mal DNA (rDNA) arising from the 100-200 tandemly repeated copies in the gen ome. We show here that mutation of the FOB1 gene slows the generation of th ese circles and thus extends life span. Fob1p is known to create a unidirec tional block to replication forks in the rDNA. We show that Fob1p is a nucl eolar protein, suggesting a direct involvement in the replication fork bloc k. We propose that this block can trigger aging by causing chromosomal brea ks, the repair of which results in the generation of rDNA circles. These fi ndings may provide a novel link between metabolic rate and aging in yeast a nd, perhaps, higher organisms.