We tested whether Fob1 was required for age-associated LOH at the MET15 locus. In young cells, fob1Δ led to a reduction in the MET15 LOH rate of ∼2-fold (Figure 3), but this rate was still significantly higher than the LOH rate on chromosome IV, suggesting that other mechanisms must contribute to the hotspot activity affecting MET15. When we measured MET15 LOH in aging fob1Δ cells we found the age-associated increase in rate of LOH was completely suppressed (Figure 3). This result indicated that Fob1 activity is required for this aging phenotype and suggests that Fob1-mediated DSBs are a critical intermediate for these LOH events.
