A Possible Mechanism for Hyperthermic Radiosensitization Mediated through Hyperthermic Lability of Ku Subunits in DNA-Dependent Protein Kinase

Author: Matsumoto Y.   Suzuki N.   Sakai K.   Morimatsu A.   Hirano K.   Murofushi H.  

Publisher: Elsevier

ISSN: 0006-291X

Source: Biochemical and Biophysical Research Communications, Vol.234, Iss.3, 1997-05, pp. : 568-572

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Abstract

DNA-dependent protein kinase (DNA-PK), composed of p470 catalytic subunit and p85/p70 heterodimer of Ku autoantigen, is considered a critical enzyme in DNA double-strand break repair. We purified DNA-PK from human leukaemic MOLT-4 cells by successive column chromatography and separated into p470 and Ku subunits by ultracentrifugation in glycerol gradient. We studied hyperthermic stability of DNA-PK holoenzyme and its separated subunits to test a possible role of DNA-PK in hyperthermic radiosensitization. DNA-PK was found to lose its activity rapidly at hyperthermic 44#°C, and further, Ku subunits instead of p470 catalytic subunits were found to be sensitive to hyperthermia. These results indicate a possibility that hyperthermic radiosensitization is mediated through the heat lability of Ku subunits of DNA-PK, impairing repair of radiation-induced double-strand break of DNA.

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