DEFECTIVE MODULATION OF DOUBLE-STRAND BREAK REPAIR IN ATAXIA-TELANGIECTASIA CELLS BY GAMMA-RADIATION

Ataxia telangiectasia (AT) cells are defective in responding to damage induced by ionizing radiation. To study the modulation of double-stra nd break (DSB) repair by ionizing radiation and a defect in such modul ation in AT cells, we compared processing of linearized shuttle vector pZ189 (linear DNA) by unirradiated or gamma-irradiated normal and AT lymphoblast hosts. The linear DNA processed in unirradiated AT and nor mal host cells yielded similar mutation frequencies in the supF-tRNA t arget gene. Irradiation of normal but not AT host cells decreased plas mid mutation frequency 2-fold if transfection occurred immediately. Ho wever, if transfection occurred 2 h after host cell irradiation, mutat ion frequencies increased 2-fold above those in unirradiated controls in both normal and AT hosts. DSB rejoining capability, based on the ra tio of the number of progeny arising from equal amounts of linear DNA and supercoiled, undamaged pZ189, was 25- to 50-fold higher in normal than in AT hosts when both were unirradiated. Irradiation decreased DS B rejoining capability 2- to 5-fold in normal hosts but did not alter that of AT hosts. These findings demonstrate that AT cells normally re join DSBs as accurately as normal cells but do so less often, and that AT cells are defective in modulation of DSB rejoining by ionizing rad iation, (C) 1998 by Radiation Research Society.