We next monitored the effect of FEN1/DNA-PKcs co-inhibition on glioma cells cycle progression and cell growth and observed that combined depletion of FEN1 and DNA-PKcs resulted in a reduction in EdU incorporation compared with cells depleted of either protein alone (Fig. 6a and b), suggesting that the synthetic interaction between FEN1 and DNA-PKcs counteracts DNA replication upon endogenous stress-induced impaired cell cycle progression by inhibiting DNA synthesis in the S phase. Here, PRKDC is linked to central nervous system cancer.