Murnane J P, Painter R B
Proc Natl Acad Sci U S A. 1982 Mar;79(6):1960-3. doi: 10.1073/pnas.79.6.1960.
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.
人类遗传性疾病共济失调毛细血管扩张症(A-T)中的突变亚型是通过一种监测DNA合成缺陷互补作用的检测系统来分类的。先前在A-T细胞中已观察到DNA合成异常,既表现为暴露于电离辐射后未能立即抑制DNA合成,也表现为其S期延长。聚乙二醇介导的细胞融合和放射自显影技术,与通过荧光彩色微球对不同A-T细胞群体进行选择性鉴定相结合,以确定各种A-T细胞组合的互补能力。通过未受辐射的异核体中DNA合成速率提高30 - 40%以及异核体经X射线照射后出现正常的DNA合成抑制现象,确定了五个互补组。这些现象之间观察到的相关性表明,A-T细胞中的缺陷涉及DNA合成起始方面的问题。