DEFECTS IN THE KINETICS OF THE REPAIR OF DNA DOUBLE-STRAND BREAKS ANDINHIBITION OF DNA-SYNTHESIS IN THE ATAXIA-TELANGIECTASIA AT5BI-VA CELL-LINE - COMPARISON TO A CORRECTED HYBRID, ATXBC

The nature of the primary biochemical defect in the human radiosensiti ve and cancer-prone syndrome, ataxia telangiectasia (AT), has remained obscure despite many efforts to elucidate it. In this study, AT compl ementation group D cells and a nearly isogenic corrected AT-hamster hy brid derivative have been analyzed for induction and repair of initial double-strand breaks (DSBs) after exposure to ionizing radiation, usi ng a sensitive field-inversion electrophoresis technique, Results sugg esting that initial levels of damage are the same in these two cell ty pes, but indicating differences in the fast component of DNA repair, h ave been compared and correlated with those resulting from a study of the radioresistant DNA synthesis defect and its correction in the same cell lines. These measurements show that the radioresistant phenotype of the substantially corrected AT-hamster hybrid correlates with its higher level of fast-component DSB repair and higher level of inhibiti on of DNA synthesis, but that the initial damage induction does not co ntribute to the phenotype. We propose that the AT gene product(s) is l ikely to act early in a signaling pathway which controls both DNA repa ir and progression of cells through the phases of the cell cycle in re sponse to ionizing radiation. (C) 1995 by Radiation Research Society