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Updated: Feb 14, 2026

Electromechanical Assessment of Optogenetically Modulated Cardiomyocyte Activity
Published on: March 5, 2020
NOTCH1 modulates activity of DNA-PKcs
Marek Adamowicz1, Fabrizio d'Adda di Fagagna2, Jelena Vermezovic3
1IFOM Foundation - FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy; Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RH, UK.
Abstract:
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) controls one of the most frequently used DNA repair pathways in a cell, the non-homologous end joining (NHEJ) pathway. However, the exact role of DNA-PKcs in NHEJ remains poorly defined. Here we show that NOTCH1 attenuates DNA-PKcs-mediated autophosphorylation, as well as the phosphorylation of its specific substrate XRCC4. 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.
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