Rejoining of Double Strand Breaks in Normal Human and Ataxia-telangiectasia Fibroblasts after Exposure to⁶⁰Co γ-rays,²⁴¹Am α-particles or Bleomycin

Abstract

The rejoining of DNA double strand breaks (dsb) induced by 60Co gamma-rays, 241Am alpha-particles or bleomycin was measured by neutral filter elution. In agreement with their colony-forming ability, ataxia-telangiectasia cells (AT2BE) and normal fibroblasts exhibited similar dsb rejoining capacity following alpha-irradiation, but showed marked differences in the rejoining kinetics of dsb induced by gamma-rays or bleomycin.

ATM, a central controller of cellular responses to DNA damage

“…4,6,7 Although earlier attempts failed to reveal any significant defect in double-strand break (DSBs) joining at short times after irradiation, Cornforth and Bedford 8 demonstrated the presence of residual chromosomal breaks in DNA from A-T cells post-irradiation using the premature chromosome condensation assay. Further support for a defect in DSB rejoining in A-T was provided by Coquerelle et al,9 who demonstrated that rejoining of radiation-induced DSBs was slower in A-T fibroblasts than in controls. Consistent with this, it was revealed that the overall extent of repair of breaks did not exceed 90% of control cells.…”

A DNA repair defect in a radiation-sensitive clone of a human bladder carcinoma cell line

“…Low repair fidelity and radioresistant DNA synthesis are both reported features of A-T (Cox et al, 1986;Debenham et al, 1988a;Painter, 1981). A-T cells have no defect in dsb rejoining (Lehmann, 1982) with one reported exception (Coquerelle et al, 1987).In a previous report (McMillan & Holmes, 1991), the initial DNA damage, measured by neutral filter elution, was found to be the same in clone S40b and the parent line, MGH-Ul. To investigate the possibility of a repair defect in S40b we have now looked at DNA repair under two broad headings: (1) the rate and extent of dsb rejoining (2) repair fidelity.…”

“…Low repair fidelity and radioresistant DNA synthesis are both reported features of A-T (Cox et al, 1986;Debenham et al, 1988a;Painter, 1981). A-T cells have no defect in dsb rejoining (Lehmann, 1982) with one reported exception (Coquerelle et al, 1987).…”

An anti-sense construct of full-length ATM cDNA imposes a radiosensitive phenotype on normal cells

“…The exact cause of the radiosensitivity in A-T cells remains unknown but there is evidence that the rejoining of g-radiation-induced double strand breaks is slower in A-T ®broblasts (Coquerelle et al, 1987). Other reports demonstrate the continuing presence of residual double-strand breaks in DNA in A-T cells at 24 ± 72 h post-irradiation (Cornforth and Bedford, 1985;Foray et al, 1997).…”