NOTCH1 modulates activity of DNA-PKcs

Surprisingly, NOTCH1-expressing cells do not display any significant impairment in the DNA damage repair, nor cellular survival, and remain sensitive to small molecule DNA-PKcs inhibitor. Additionally, in vitro DNA-PKcs kinase assay shows that NOTCH1 does not inhibit DNA-PKcs kinase activity, implying that NOTCH1 acts on DNA-PKcs through a different mechanism. Together, our set of results suggests that NOTCH1 is a physiological modulator of DNA-PKcs, and that it can be a useful tool to clarify the mechanisms by which DNA-PKcs governs NHEJ DNA repair.