Replication stress-induced endogenous DNA damage drives cellular senescence induced by a sub-lethal oxidative stress.

ABSTRACT: Although oxidative stress has been shown to induce senescence and replication stress independently, no study has implicated unresolved replication stress as the driver for cellular senescence in response to oxidative stress. Using cells exposed to increasing concentrations of hydrogen peroxide, we show that sub-lethal amount of exogenous hydrogen peroxide induces two waves of DNA damage. The first wave is rapid and transient while the second wave coincides with the cells transition from the S to the G2/M phases of cell cycle. Subsequently, cells enter growth arrest accompanied by the acquisition of senescence-associated characteristics. Furthermore, a p53-dependent decrease in Rad51, which is associated with the formation of DNA segments with chromatin alterations reinforcing senescence, a

SUBMITTER: Venkatachalam G 

PROVIDER: S-EPMC5737622 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature