Abstract
Mutant subtypes in the human genetic disease ataxia-telangiectasia (A-T) were classified by means of an assay system that monitors complementation of defects in DNA synthesis. Anomalies in DNA synthesis have been observed previously in A-T cells, both in their failure to inhibit DNA synthesis immediately after exposure to ionizing radiation and in their prolonged S phase. Polyethylene glycol-mediated cell fusion and autoradiography were combined with selective identification of different A-T cell populations by fluorescent colored microspheres to determine complementation capabilities of various A-T cell combinations. Five complementation groups were identified by both a 30-40% increase in the rate of DNA synthesis in unirradiated heterokaryons and the appearance of normal inhibition of DNA synthesis after x-irradiation of heterokaryons. The correlation observed between these phenomena suggests that the defects in A-T cells involve problems in initiation of DNA synthesis.
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