| Ataxia-telangiectasia (A-T) is an inherited disease associated with cancer risk, immune disfunction, genetic instability and radiation sensitivity. As part of a larger project to identify the A-T gene(s), I have isolated several genes that complement phenotypic defects of a complementation group D A-T fibroblast line (GM5849).;A human cDNA library contained in an Epstein-Barr virus-based episomal expression vector was transfected into A-T fibroblasts. ;9 unrelated cDNAs, ranging in size from 0.8kb to 8.6kb, were rescued from 19 streptonigrin;These are the first reported human cDNAs to complement multiple phenotypes in A-T cells. One of these cDNAs may represent the AT-D gene. Alternatively, since none of the cDNAs mapped to the known A-T region on 11q23, they may represent new genes involved in the regulation of DNA damage response whose over-expression suppresses the A-T phenotype.;The S. cerevisiae RAD3 gene was also found to complement the mutagen sensitivity of A-T fibroblasts. The RAD3 gene complemented streptonigrin sensitivity and partially complemented X-ray sensitivity in 6 of 13 GM5849 transformants. No decrease was observed in rates of recombination in mutagen-resistant RAD3 transformants. The Rad3 protein is a homolog of the human gene ERCC2, which complements UV-sensitivity in Xeroderma Pigmentosa group D cells (Flejter, 1992). |
