HOW SELENIUM MODIFIES CROSS-TALK BETWEEN THE PIKK FAMILY AND INSIGHTS ON THE REGULATION OF DNA-PKcs

Thumbnail Image
Files
Publication or External Link
Date
2009
Authors
Rocourt, Caroline
Advisor
Cheng, Wen-Hsing
Citation
DRUM DOI
Abstract
We recently found that ATM is required for a selenium-induced senescence response in non-cancerous cells. We hypothesize the selenium-induced DNA damage response modifies ATM and DNA-PKcs cross-talk. Phospho-specific antibodies against ATM and DNA-PKcs were used to follow the phosphorylation events after selenium treatment in normal human cells and two human cancer cell lines. Results from immunofluorescence analysis showed that selenium treatment induces hyperphosphorylation of DNA-PKcs at T2647 and S2056 in non-cancerous MRC-5 cells but not in U-2 OS cancer cells. Further studies in MRC-5 cells treated with an ATM kinase inhibitor, KU 55933, showed attenuation of the selenium-induced DNA-PKcs phosphorylation at both foci, whereas pre-treatment with a DNA-PKcs kinase inhibitor, NU 7026, does not prevent ATM phosphorylation at S1981, an event leading to ATM pathway activation. These results give evidence that DNA-PKcs and ATM have a cooperative role in the DNA damage response pathway.
Notes
Rights