Expression of fragile site on the human X chromosome in somatic cell hybrids between human fragile X cells and thymidylate synthase-negative mouse mutant cells.
Fragile sites appear to be associated with a higher rate of breakage and specific chromosome rearrangement in cancer. A fragile site located on the human X chromosome at band Xq27 is known to be expressed under conditions of thymidylate stress. In order to obtain a model cell system suitable for studying the mechanism of expression of the fragile X site, interspecific somatic cell hybrids were constructed by cell fusion between human skin fibroblasts derived from a male patient with fragile X-linked mental retardation and thymidylate synthase-negative mouse mutant cells. The primary isolated hybrid clones were thymidine-prototrophic and expressed the fragile X site under conditions of thymidylate stress caused by 5-fluoro-2'-deoxyuridine treatment. In a thymidine-auxotrophic hybrid clone segregated from a thymidine-prototrophic hybrid clone, the expression of the fragile X site was induced in thymidylate stress conditions achieved by thymidine deprivation alone. This result provides direct evidence that expression of the fragile X site is dependent upon a lowered supply of thymidylate.
D000818:Animals; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D012729:Sex Chromosome Aberrations / Q000235:genetics*; D013940:Thymidylate Synthase / Q000172:deficiency*
D013940:Thymidylate Synthase