DNA strand breakage repair in ataxia telangiectasia fibroblast-like cells

Human DNA repair systems: An overview

“…The first human repair deficiency disease identified was xeroderma pigmentosum (XP) [Jung and Bantle, 1971;Stich, 1975], a hereditary deficiency in any of several nucleotide excision repair genes. Other human disorders related to defective DNA repair or defective cellular responses to DNA damage include trichothiodystrophy [Rebora and Crovato, 1987], Cockayne syndrome, Fanconi's anemia [Poon et al, 1975], ataxia telangiectasia [Vincent et al, 1975], Bloom's syndrome [Inoue et al, 1977], and hereditary nonpolypopsis colorectal cancer (HNPCC) Bronner et al, 1994]. Clinical disease arising from defects in DNA repair is complex and often severe.…”

An apparent correlation between the inhibition of induced ornithine decarboxylase activity by ? radiation and the capacity for DNA repair synthesis in normal and ataxia telangiectasia human fibroblasts: No correlation with cell survival

“…Various other lesions in DNA are efficiently repaired in AT cells. These include DNA single-strand breaks [17], apurinic sites [18], and 5,6-dihydroxydihydrothymine [12], as well as purine methylation adducts [19]. Thus, the underlying cause for AT radiosensitivity may be a deficiency in a DNA repair mechanism not identified so far, or in another, unrelated structure.…”

The effect of bleomycin on DNA synthesis in ataxia telangiectasia lymphoid cells

“…Concomitant with decreased DNA synthesis following irradiation, an increase in the level of the enzyme poly-(ADP-ribose) polymerase in normal, but not AT cells, has been reported [Edwards and Taylor, 19801. This enzyme is synthesized in response to DNA damage and may function in the recovery from this event. It has been suggested that the underlying defect in AT may be associated with inefficient repair of a small number of critical DNA strand breaks, not detectable by currently available techniques [Lehmann, 1977; Paterson and Smith, 19791. But, since both the induction and repair of radiation as well as BLM induced DNA strand breaks are similar in normal and AT cells [Taylor et al, 1975;Vincent et al, 1975;Paterson et al, 1976; Fornace and Little, 19801, this process is probably not responsible for the differential inhibition of DNA synthesis. Moreover, the similar response to y-irradiation and BLM exhibited by cells from six "excisionproficient" and two "excision-deficient" AT patients (as measured by y-ray-induced repair synthesis) [Lavin and Kidson, 1978;Taylor, 1978; Smith and Paterson, 1980;deWit et al, 19811 suggests that such resistance to DNA synthesis inhibition may not be related to repair capacity.…”