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DNA-PK suppresses a p53 independent apoptotic response to DNA damage

Gurley, Kay E. and Moser, Russell and Gu, Yansong and Hasty, Paul and Kemp, Christopher J. (2009) DNA-PK suppresses a p53 independent apoptotic response to DNA damage. EMBO Reports, 10 (1). pp. 87-93. ISSN 1469 - 221X

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Article URL: http://www.nature.com/embor/journal/vaop/ncurrent/...

Abstract

p53 is required for DNA damage induced apoptosis, which is central to its function as a tumor suppressor. Here we show 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-PK. Intestinal crypt cells from p53 nullizygous mice were resistant to radiation induced apoptosis, while apoptosis in DNAPKcs/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/p53 or ATM/p53 double null mice. Further, it was associated with increased phospho-Chk2, and cleaved caspases 3 and 9, the latter indicating engagement of the intrinsic apoptotic pathway. This demonstrates 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.

Item Type: Article
Additional Information: This article is available to subscribers only at the Article URL above.
DOI: 10.1038/embor.2008.214
PubMed ID: 19057578
PMCID: PMC2613202
Grant Numbers: RO1 CA070414
Keywords or MeSH Headings: Animals; *Apoptosis; DNA Damage/*genetics; DNA-Activated Protein Kinase/deficiency/genetics/*metabolism; *Down-Regulation; Mice; Mice, Knockout; Tumor Suppressor Protein p53/deficiency/genetics/*metabolism
Subjects: Cellular and Organismal Processes > Genetic processes > DNA damage and repair
Cellular and Organismal Processes > Cell Physiology > Cell death
Depositing User: Library Staff
Date Deposited: 10 Dec 2008 21:33
Last Modified: 14 Feb 2012 14:43
URI: http://authors.fhcrc.org/id/eprint/90

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