| First Author | Gurley KE | Year | 2009 |
| Journal | EMBO Rep | Volume | 10 |
| Issue | 1 | Pages | 87-93 |
| PubMed ID | 19057578 | Mgi Jnum | J:157375 |
| Mgi Id | MGI:4430714 | Doi | 10.1038/embor.2008.214 |
| Citation | Gurley KE, et al. (2009) DNA-PK suppresses a p53-independent apoptotic response to DNA damage. EMBO Rep 10(1):87-93 |
| abstractText | p53 is required for DNA damage-induced apoptosis, which is central to its function as a tumour suppressor. Here, we show that the apoptotic defect of p53-deficient cells is nearly completely rescued by inactivation of any of the three subunits of the DNA repair holoenzyme DNA-dependent protein kinase (DNA-PK). Intestinal crypt cells from p53 nullizygous mice were resistant to radiation-induced apoptosis, whereas apoptosis in DNA-PK(cs)/p53, Ku80/p53 and Ku70/p53 double-null mice was quantitatively equivalent to that seen in wild-type mice. This p53-independent apoptotic response was specific to the loss of DNA-PK, as it was not seen in ligase IV (Lig4)/p53 or ataxia telangiectasia mutated (Atm)/p53 double-null mice. Furthermore, it was associated with an increase in phospho-checkpoint kinase 2 (CHK2), and cleaved caspases 3 and 9, the latter indicating engagement of the intrinsic apoptotic pathway. This shows that there are two separate, but equally effective, apoptotic responses to DNA damage: one is p53 dependent and the other, engaged in the absence of DNA-PK, does not require p53. |
