Open AccessComplementation of the defects of DNA synthesis in irradiated and unirradiated ataxia-telangiectasia cells.
Author(s) -
John P. Murnane,
Robert B. Painter
Publication year - 1982
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.79.6.1960
Subject(s) - complementation , ataxia telangiectasia , dna synthesis , dna , microbiology and biotechnology , cell fusion , biology , heterokaryon , mutant , dna damage , cell , genetics , gene
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.