This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burgman, P. Articles by Li, G. C. Search for Related Content PubMed PubMed Citation Articles by Burgman, P. Articles by Li, G. C.

Heat Inactivation of Ku Autoantigen: Possible Role in Hyperthermic Radiosensitization¹

Departments of Medical Physics and Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10021 [P. B., H. O., G. C. L.], and Life Science Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 [S. P., D. J. C.]

Heat shock prior, during, or immediately after ionizing radiation synergistically increases cell killing, a phenomenon termed hyperthermic radiosensitization. Recently, we have shown a constitutive DNA-binding factor in rodent cells that is inactivated by heat shock to be identical to Ku autoantigen. Ku, consisting of an M_r 70,000 (Ku70) and an M_r 86,000 (Ku80) subunit, is a heterodimeric nuclear protein and is the DNA-binding regulatory component of the mammalian DNA-dependent protein kinase DNA-PK. Recent genetic and biochemical studies indicate the involvement of Ku and DNA-PK in DNA double-strand break repair and V(D)J recombination. On the basis of these findings, we propose that heat-induced loss of the DNA-binding activity of Ku may lead to hyperthermic radiosensitization. To test this hypothesis, we examined and compared the DNA-binding activity of Ku, the DNA-PK kinase activity, and hyperthermic radiosensitization in rodent cells immediately after heat shock and during post-heat shock recovery at 37°C. Our results show that the heat-induced loss of Ku-DNA binding activity correlates well with an increased radiosensitivity of the heat-shocked cells, and furthermore, the loss of synergistic interaction between heat and radiation parallels the recovery of the DNA-binding activity of Ku. On the other hand, the heat-induced decrease of DNA-PK activity did not correlate with hyperthermic radiosensitization. Our data, for the first time, provide evidence for a role of Ku protein in modulating the cellular response to combined treatments of heat shock and ionizing radiation.

¹ This work was supported in part by Grants CA31397, CA56909 (to G. C. L., P. B., and H. O.), and CA50519 (to D. J. C.) from the NIH and the Department of Energy (to D. J. C.).

² To whom requests for reprints should be addressed, at Memorial Sloan Kettering Cancer Center, Box 72, 1275 York Avenue, New York, NY 10021. Phone: (212) 639-6028; Fax: (212) 639-2611; E-mail: g-li@ski.mskcc.org.

Received 4/15/97. Accepted 5/23/97.

This article has been cited by other articles:

				F. Fernandez-Madrid, N. Tang, H. Alansari, J. L. Granda, L. Tait, K. C. Amirikia, M. Moroianu, X. Wang, and R. L. Karvonen Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer Cancer Res., August 1, 2004; 64(15): 5089 - 5096. [Abstract] [Full Text] [PDF]

				R. A. El-Awady, E. Dikomey, and J. Dahm-Daphi Heat effects on DNA repair after ionising radiation: hyperthermia commonly increases the number of non-repaired double-strand breaks and structural rearrangements Nucleic Acids Res., May 1, 2001; 29(9): 1960 - 1966. [Abstract] [Full Text] [PDF]

				M. Giampuzzi, G. Botti, M. Di Duca, L. Arata, G. Ghiggeri, R. Gusmano, R. Ravazzolo, and A. Di Donato Lysyl Oxidase Activates the Transcription Activity of Human Collagene III Promoter. POSSIBLE INVOLVEMENT OF Ku ANTIGEN J. Biol. Chem., November 10, 2000; 275(46): 36341 - 36349. [Abstract] [Full Text] [PDF]