The rare mutations and altered expression levels of key NHEJ and HDR proteins, mainly Ku70/80, DNA-PK, Artemis, Ligase IV, XRCC4, XLF, MRE11, RAD51, RPA and RAD52 can lead to predisposition to cancer, whereas increased capacity of DNA repair and DDR can be clinically exploited by targeting repair pathways to overcome resistance and enhance chemo- or radiosensitivity in cancer patients (5, 71–75). The gene discussed is RAD51; the disease is cancer.