Pathologic Replication-Independent Endogenous DNA Double-Strand Breaks Repair Defect in Chronological Aging Yeast

Reduction of physiologic replication-independent endogenous DNA double strand breaks (Phy-RIND-EDSBs) in chronological aging yeast increases pathologic RIND-EDSBs (Path-RIND-EDSBs). Path-RIND-EDSBs can occur spontaneously in non-dividing cells without any inductive agents, and they must be repaired immediately otherwise their accumulation can lead to senescence(definition). If yeasts have DSB repair defect, retention of Path-RIND-EDSBs can be found. Previously, we found that Path-RIND-EDSBs are not only produced but also retained in chronological aging yeast. Here, we evaluated if chronological aging yeasts have a DSB repair defect. We found a significant accumulation of Path-RIND-EDSBs around the same level in aging cells and caffeine treated cells and at a much higher level in the DSB repair mutant cells. Especially in the mutant, some unknown sequence was found inserted at the breaks. In addition, % difference of cell viability between HO induced and non-induced cells was significantly greater in aging cells. Our results suggested that RIND-EDSBs repair efficiency declines, but is not absent, in chronological aging yeast which might promote senescence phenotype. When a repair protein is deficient, an alternative pathway might be employed or an end modification process might occur as inserted sequences at the breaks were observed. Restoring repair defects might slow down the deterioration of cells from chronological aging.