Fig. 7

The working model for APE1 contributes to therapeutic resistance following oxidative stress by promoting DDR and NHEJ repair. APE1, via the endonuclease activity, initiates the DSBs formation at the early phase post-oxidative agent exposure, which is a prerequisite for the activation the subsequently DDR and NHEJ repair. In addition, APE1 deficiency attenuates NHEJ capacity by increasing the ubiquitination and degradation of Artemis. Overall, APE1 deficiency results in numerous DSBs accumulation and triggers the activation of ATM at the late phase, inhibition of the ATM significantly promotes synergistic lethality with oxidative damage in APE1-deficient cells