Taking advantage of the requirement for Fob1, we investigated potential mechanisms leading to the age-associated LOH phenotype. Disruption of cohesion, via the deletion of the cohibins LRS4 and CSM1, was eliminated as a potential mechanism because it leads to Fob1-independent LOH events. While SIR2 deletion generated Fob1-dependent LOH events in young cells, the LOH events observed in this strain were significantly biased towards a non-reciprocal pathway compared to the LOH events generated in young or old wild type cells. Additionally, when sir2Δ cells were aged they also displayed an age-associated increase in LOH in the longest-lived fraction of the population. Both the difference in repair bias and presence of an age-associated increase in LOH independent of SIR2 suggests that loss of Sir2 function in aging cells is likely not the driver of age-associated LOH.
