title: Reduced induction of P53 protein by gamma-irradiation in ataxia telangiectasia cells without constitutional mutations in exons 5, 6, 7, and 8 of the p53 gene.
abstract: Ataxia telangiectasia (AT) is an autosomal recessive disease of childhood with several phenotypic characteristics. One of the hallmarks of this syndrome is its hypersensitivity to ionizing radiation, which is believed to be due to defects in DNA repair/processing. In addition to radio-resistant DNA synthesis, both fibroblasts and lymphoblastoid cell lines derived from these patients have been shown to have an impaired G1 arrest and prolonged G2 accumulation of cells indicating a defect in the regulation of cell cycle after irradiation. Since the (tumor suppressor) p53 protein has been reported to participate in the regulation of G1 arrest after irradiation, the possibility of p53 gene mutation and deregulating cell cycle in AT needed to be examined. We used the PCR amplification and DNA sequencing methods to detect mutations in the hypermutable exons (5-8) of germline p53 in fibroblast cells from 3 AT homozygotes. No mutation was found in any of these exons. In order to determine the role of the p53 protein in G1 arrest, its levels were measured before and after gamma-irradiation by flow cytometry in both AT and normal cells. Radiation-induced p53 protein levels in the AT cells varied from 6 to 60% compared to the normal cells, indicating a reduced induction of the protein in AT. These results suggest that mutation in the AT gene affects the p53 induction by irradiation and may, thus, alter the cell cycle regulation in the AT patients.
authors.affiliation: Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: N
authors.initials: N
authors.lastname: Nasrin
authors.forename: M
authors.initials: M
authors.lastname: Kunhi
authors.forename: M
authors.initials: M
authors.lastname: Einspenner
authors.forename: S
authors.initials: S
authors.lastname: al-Sedairy
authors.forename: M
authors.initials: M
authors.lastname: Hannan
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002453:Cell Cycle / Q000528:radiation effects; D002478:Cells, Cultured; D005091:Exons / Q000528:radiation effects; D005347:Fibroblasts; D005434:Flow Cytometry; D005720:Gamma Rays; D016158:Genes, p53 / Q000528:radiation effects*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000528:radiation effects*
chemical_list: D016159:Tumor Suppressor Protein p53