Abstract
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. 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.
Highlights
We previously proved that pathologic endogenous DNA double-strand breaks (EDSBs) can occur spontaneously, even without exposure to radiation or DNA damaging agents, and were excessively detectable when non-dividing cells had functional double-strand breaks (DSB) repair defects
Our results showed that its Path-RIND-EDSBs level increased slightly: nej1 results were very different from other mutant strains and this was in accord with (Thongsroy et al, 2013)
Our data showed an accumulation of Path-RIND-EDSBs in aging cells and cells with repair defects either chemically defected or genetically defected
Summary
We previously proved that pathologic endogenous DNA double-strand breaks (EDSBs) can occur spontaneously, even without exposure to radiation or DNA damaging agents, and were excessively detectable when non-dividing cells had functional double-strand breaks (DSB) repair defects In other words, they are produced independently of replication, we named them pathologic replication-independent EDSBs (Path-RIND-EDSBs) (Thongsroy et al, 2018). Previous studies showed evidence that a reduction of Phy-RIND-EDSBs decreased cell viability and promoted genome instability (Thongsroy et al, 2018) They are preferentially located in hypermethylated genome regions, were retained in facultative heterochromatin in human cells, preferentially occurred immediately after certain 4bp sequence and were prevented from occurring after certain 4-bp in yeast (Kongruttanachok et al, 2010; Pongpanich et al, 2014)
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