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J Biol Chem, Vol. 275, Issue 9, 6651-6656, March 3, 2000

Ionizing Radiation Exposure Results in Up-regulation of Ku70 via a p53/Ataxia-Telangiectasia-mutated Protein-dependent Mechanism*

Kevin D. BrownDagger §, Tamara A. LataxesDagger , Sanjeev Shangary||, Jennifer L. ManninoDagger , Jason F. GiardinaDagger , Jiandong Chen§**Dagger Dagger , and R. Baskaran||

From the Dagger  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

Genome damaging events, such as gamma -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 gamma -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.

To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, LSU Medical Center, 1901 Perdido St., MEB Rm. 7101, New Orleans, LA 70112. Tel.: 504-568-2090; Fax: 504-568-3370; E-mail: kbrown1@lsumc.edu.

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


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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