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PMID:29482073
| Citation |
Adamowicz, M, d'Adda di Fagagna, F and Vermezovic, J (2018) NOTCH1 modulates activity of DNA-PKcs. Mutat. Res. 808:20-27 |
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| 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. |
| Links |
PubMed Online version:10.1016/j.mrfmmm.2018.01.003 |
| Keywords |
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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0031953: negative regulation of protein autophosphorylation |
ECO:0000314: |
P |
Figure 1C and S1C, NOTCH1 impairs DNA-PKcs autophosphorylation (Ser2065) to a similar, although slightly lower, extent as the small molecule DNA-PKcsi. |
complete | ||||
Notes
See also
References
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