We observed a significant increase in both reciprocal and non-reciprocal recombination events, which likely report two different routes of DSB repair. Reciprocal LOH events likely result from strand invasion leading to Holliday junction formation and resolution with crossing over [49], while the non-reciprocal events we observed are consistent with break-induced replication (BIR) initiated within the rDNA and propagated to the telomere of chromosome XII [17], [49]. These recombination events also differ from the age-associated genomic instability described in cells that have lost respiration competence [11], where LOH events were almost uniformly non-reciprocal. The phenotypic differences between the earlier studies and those reported here support the conclusion that a different mechanism leads to age-associated LOH events in cells that maintain respiration competence. Because most eukaryotic cells cannot tolerate the loss of mtDNA, it is likely that the findings we report here about genomic instability may be relevant to the aging process in other organisms.
