While the fob1Δ strain permitted us to determine the utility of our ERC measurements with age, it was not useful for examining the effect of ERC accumulation on LOH because, as shown above, Fob1 is required for the age-associated LOH events. For this, we examined a genetic background that could reduce ERC accumulation independently of Fob1. Deletion of BUD6 has been reported to disrupt the asymmetric segregation of ERCs, resulting in extended life span and a prediction of reduced ERC accumulation in mother cells [45]. Consistent with this prediction, we found that deletion of bud6Δ reduced the level of ERCs throughout the life span of a population. The bud6Δ cells showed a 50% reduction in ERCs after 50 hours of replicative aging: A level that was achieved in wild type populations aged for only 26 hours (Figure 8B). Remarkably, we saw no change in the age-associated increase in LOH rate at MET15 in the bud6Δ strain (Figure 8C). This indicated that in the presence of Fob1 activity, a 50% reduction in ERC accumulation was not sufficient to suppress age-associated LOH.
