RADIORESISTANT DNA-SYNTHESIS IN SV40-IMMORTALIZED ATAXIA-TELANGIECTASIA FIBROBLASTS

Ataxia telangiectasia (AT) is an autosomal recessive disease, characte rized by both neurological disorders and a high incidence of early-ons et cancers. On a cellular level, cellular radiosensitivity and radiore sistant DNA synthesis are the hallmarks of AT. While expression of cel lular radiosensitivity varies somewhat among affected individuals, rad ioresistant DNA synthesis is seen consistently and, in fact, is the on ly end point used for assigning individuals to genetic complementation groups. For this reason, complementation-group-specific correction of radioresistant DNA synthesis in AT cells has long been thought to be an absolute requirement for confirmation of a bona fide clone of an AT gene, Since primary AT cells grow poorly in culture, SV40-immortalize d AT fibroblasts are the usual recipients of transfected DNA in these studies, In experiments reported here, we demonstrate that SV40-immort alized AT fibroblasts have significantly reduced radioresistant DNA sy nthesis compared to primary AT fibroblasts, and their response to radi ation is more like normal cells, in that both the radiosensitive and r adioresistant components appear to be present. This suggests that ther e may be an interaction between SV40 proteins and the AT gene product or its downstream elements. This partial ''complementation'' of radior esistant DNA synthesis in SV40-immortalized AT cells complicates compl ementation cloning strategies, and should be considered when terminall y screening putative AT gene clones by analysis of radioresistant DNA synthesis. (C) 1995 by Radiation Research Society