Expression cloning of multiple human cDNAs that complement the phenotypic defects of ataxia-telangiectasia group D fibroblasts

摘要: Ataxia-telangiectasia (A-T) is an inherited human disease of unknown etiology associated with neurologic degeneration, immune dysfunction, cancer risk, and genetic instability. A-T cells are sensitive to ionizing radiation radiomimetic drugs, offering the possibility cloning genes by phenotypic complementation. We have used this sensitivity isolate first cDNAs reported complement in culture. Complementation group D fibroblasts were transfected episomal vector-based cDNA library, approximately 610,000 resultant transformants treated drug streptonigrin-resistant, nine unrelated recovered from 29 surviving streptonigrin-resistant clones. Five mapped, but none localized 11q23, site complementation A C loci. Four mapped conferred mutagen resistance on secondary transfection. One was identified as a fragment dek, gene involved acute myeloid leukemia. The dek pCAT4.5, 4.5-kb that 17p11, independently complemented three different abnormalities (mutagen sensitivity, hyper-recombination, radio-resistant DNA synthesis). pCAT4.5 did not fibroblast line, suggesting it represents candidate for A-T. Our results indicate alone insufficient evidence prove gene. complementing may represent previously uncharacterized function same pathway does product(s) regulation cellular responses damage.