| First Author | Woo RA | Year | 1998 |
| Journal | Nature | Volume | 394 |
| Issue | 6694 | Pages | 700-4 |
| PubMed ID | 9716137 | Mgi Jnum | J:119886 |
| Mgi Id | MGI:3703415 | Doi | 10.1038/29343 |
| Citation | Woo RA, et al. (1998) DNA-dependent protein kinase acts upstream of p53 in response to DNA damage. Nature 394(6694):700-4 |
| abstractText | The tumour suppressor p53 becomes activated as a transcription factor in response to DNA damage, but the mechanism for this activation is unclear. A good candidate for an upstream activator of p53 is the DNA-dependent protein kinase (DNA-PK) that depends on the presence of DNA breaks for its activity. Here we investigate the link between DNA damage and the activation of DNA-PK and of p53. To determine whether DNA-PK is an upstream mediator of the p53 DNA-damage response, we analysed a severe combined-immunodeficiency (SCID) mouse cell line, SCGR11, and the human glioma cell line M059J . Both cell lines lack any detectable DNA-PK activity. We find that p53 is incapable of binding to DNA in the absence of DNA-PK, that DNA-PK is necessary but not sufficient for activation of p53 sequence-specific DNA binding, and that this activation occurs in response to DNA damage. Our results establish DNA-PK as a link between DNA damage and p53 activation, and reveal the existence of a mammalian DNA-damage-response pathway. |
