Although the roles of DNA-dependent protein kinase catalytic subunits (DNA-PKcs) in the non-homologous end joining (NHEJ) of DNA repair are well-recognized, the biological mechanisms and regulators by DNA-PKcs besides DNA repair, have not been clearly described. Here, we show that active DNA-PKcs caused by ionizing radiation, phosphorylated Snail1 at serine (Ser) 100, led to increased Snail1 stability. Furthermore, phosphorylated Snail1 at Ser100 reciprocally inhibited the kinase activity of DNAPKcs, resulting in an inhibition of DNA repair activity. Moreover, Snail1 phosphorylation by DNA-PKcs was involved in genomic instability and aggressive tumor characteristics. Our results describe novel cellular mechanisms that affect genomic instability, sensitivity to DNA-damaging agents, and the migration of tumor cells by reciprocal regulation between DNA-PKcs and Snail1.
Bibliographical noteFunding Information:
Acknowledgements. This work was supported by a grant of the Advanced Research Center for Nuclear Excellence (2011-0031696), and a grant of Mid-Career Researcher Program (2011-0013364) of the National Research Foundation of Korea (NRF), funded by the Korean government (MEST). This work was also supported by an Ewha Global Top5 Grant 2011 from Ewha Womans University.
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience
- Cell Biology
- Cancer Research