Abstract
Cancer cells exhibit an elevated intracellular level of reactive oxygen species (ROS) because of their accelerated metabolism, mitochondrial dysfunction, and antioxidant deficit. The oxidative stress in cancer cells may provide clinical benefits, which can be associated with a better response to anticancer therapies. Therefore, identifying the regulatory pathway of oxidative stress in cancer cells is important in the development of therapeutic targets that enhance sensitivity to ROS-generating anticancer therapies. Here, we report that nuclear receptor subfamily 1, group D, member 1 (NR1D1; Rev-erbα) inhibited DNA repair of ROS-induced DNA damage in breast cancer cells. NR1D1 interacted with poly(ADP-ribose) polymerase 1 (PARP1) and subsequently inhibited catalytic activity of PARP1. NR1D1 enhanced accumulation of DNA damage, which increased sensitivity of breast cancer cells to oxidative stress. Our findings suggest that NR1D1 could be a therapeutic target for breast cancer treatment, especially in those patients treated with ROS-inducing chemotherapeutic agents.