title: Molecular studies on the nature of the repair defect in ataxia-telangiectasia and their implications for cellular radiobiology.
abstract: We have utilized DNA transfer and recombinant DNA techniques to probe DNA double-strand break repair in the human ionizing radiation-sensitive genetic syndrome ataxia-telangiectasia (A-T). Using restriction enzyme-generated double-strand breaks in the coding sequence of a selectable gene we have detected a significantly greater frequency of mis-repair of such breaks in a permanent A-T cell line compared with cell lines of normal radiosensitivity. This mis-repair in A-T can plausibly explain many of the clinical features of the disease but was insufficiently detailed to address the broad problem of DNA repair mechanisms relevant to ionizing radiation-induced damage. To extend these observations of DNA double-strand break mis-repair we have now applied this type of repair assay to novel, de novo induced mammalian X-ray-sensitive cell lines and to appropriate Escherichia coli mutants. In both cellular systems we have now found some equivalence to the A-T repair defect. In particular, studies on one E. coli mutant have provided evidence suggesting an involvement of a topoisomerase activity in DNA double-strand break mis-repair, which may be relevant to the biochemical defect in A-T.
authors.affiliation: Division of Cell and Molecular Biology, MRC Radiobiology Unit, Chilton, Oxon, UK.
authors.forename: P G
authors.initials: PG
authors.lastname: Debenham
authors.forename: M B
authors.initials: MB
authors.lastname: Webb
authors.forename: N J
authors.initials: NJ
authors.lastname: Jones
authors.forename: R
authors.initials: R
authors.lastname: Cox
mesh_terms: D001260:Ataxia Telangiectasia; D002460:Cell Line; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004260:DNA Repair; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D006801:Humans; D010641:Phenotype; D011836:Radiation Tolerance; D014965:X-Rays
chemical_list: D004247:DNA; D004250:DNA Topoisomerases, Type II