Henderson L M, Arlett C F, Harcourt S A, Lehmann A R, Broughton B C
Proc Natl Acad Sci U S A. 1985 Apr;82(7):2044-8. doi: 10.1073/pnas.82.7.2044.
A fibroblast cell strain, 46BR, derived from an immunodeficient patient is hypersensitive to the lethal effects of a wide range of DNA-damaging agents. It is also defective in strand-break rejoining after treatment with dimethyl sulfate and UV light. The present study shows that the cells have a defect in joining Okazaki-type fragments during DNA replication, supporting the interpretation that the basic defect is in ligation of DNA strands. The baseline level of sister chromatid exchange is slightly higher than in normal cells but it does not approach that of Bloom's syndrome or dyskeratosis congenita cells. Sensitivity to the induction of sister chromatid exchange and the hypersensitivity to the lethal effects of a set of DNA-damaging agents are correlated, implying that the basic defect influences both end points in a similar manner. No 6-thioguanine-resistant mutants could be induced by either gamma- or UV-irradiation in these cells, suggesting that error-prone repair pathways for damage induced by these agents may contain a common ligation step in human cells.
从一名免疫缺陷患者身上获取的成纤维细胞系46BR，对多种DNA损伤剂的致死效应高度敏感。在用硫酸二甲酯和紫外线处理后，其链断裂重新连接也存在缺陷。本研究表明，这些细胞在DNA复制过程中连接冈崎型片段存在缺陷，支持了基本缺陷在于DNA链连接的解释。姐妹染色单体交换的基线水平略高于正常细胞，但未达到布卢姆综合征或先天性角化不良细胞的水平。对姐妹染色单体交换诱导的敏感性与对一组DNA损伤剂致死效应的高度敏感性相关，这意味着基本缺陷以类似方式影响这两个终点。在这些细胞中，γ射线或紫外线照射均无法诱导出6-硫鸟嘌呤抗性突变体，这表明这些试剂诱导损伤的易错修复途径在人类细胞中可能包含一个共同的连接步骤。
