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J Biol Chem, Vol. 275, Issue 9, 6651-6656, March 3, 2000
From the Genome damaging events, such as
Ionizing Radiation Exposure Results in Up-regulation of Ku70 via
a p53/Ataxia-Telangiectasia-mutated Protein-dependent
Mechanism*
§¶,
,
,
,
,
, and
Department of Biochemistry and Molecular
Biology, the ** Department of Microbiology, Immunology, and
Parasitology, and the § Stanley S. Scott Cancer Center,
Louisiana State University Medical Center, New Orleans, Louisiana
70112, and the
Department of Molecular Genetics and
Biochemistry, University of Pittsburgh Medical Center,
Pittsburgh, Pennsylvania 15261
-irradiation
exposure, result in the induction of pathways that activate DNA repair
mechanisms, halt cell cycle progression, and/or trigger apoptosis. We
have investigated the effects of
-irradiation on cellular levels of the Ku autoantigens. Ku70 and Ku80 have been shown to form a
heterodimeric complex that can bind tightly to free DNA ends and
activate the protein kinase DNA-PKcs. We have found that irradiation
results in an up-regulation of cellular levels of Ku70, but not Ku80, and that this enhanced level of Ku70 accumulates within the nucleus. Further, we uncovered that the postirradiation up-regulation of Ku70
utilizes a mechanism that is dependent on both p53 and damage response
protein kinase ATM (ataxia-telangiectasia-mutated); however, the
activation of DNA-PK does not require Ku70 up-regulation. These
findings suggest that Ku70 up-regulation provides the cell with a means
of assuring either proper DNA repair or an appropriate response to DNA
damage independent of DNA-PKcs activation.
*
This work was supported by Research Project Grant GMC-98564
from the American Cancer Society and by the Cancer Association of
Greater New Orleans (to K. D. B.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.

Present address: Molecular Oncology Program, H. Lee Moffit
Cancer Center, University of South Florida, Tampa, FL 33612.
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