Yet, the role of Akt in DSB repair is still highly controversial: While Akt inhibition decreased DNA-PKcs-dependent DSB repair and increased the cytotoxicity of chemotherapy and ionizing radiation in preclinical investigations16, 20, 21, 22, 23, elevated Akt activity unexpectedly also reduced D-NHEJ efficiency at least in PTEN-deficient cancer cells, presumably by inhibiting XRCC4-like factor (XLF)17. Here, AKT1 is linked to cancer.