真核生物抗损伤DNA合成

Martin F. Lavin , Alice L. Schroeder
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引用次数: 52

摘要

真核生物对电离辐射和其他有害物质敏感性的分子基础尚不清楚。虽然已经描述了大量的突变,但只有少数突变被证明在修复DNA损伤方面存在缺陷。这些突变体的一个亚群,在整个系统发育尺度上延伸的不同物种中,一个有趣的特征是存在抗损伤DNA合成。这种现象在患有遗传性失调毛细血管扩张症的个体的细胞中观察到,在紫外线照射前用氟脱氧尿嘧啶处理的HeLa细胞中,在真菌神经孢子虫突变体中,在粘菌盘状盘菌中,果蝇黑腹果蝇中,以及可能在“浪费”的小鼠突变体中。在共济失调毛细血管扩张的情况下,只观察到对电离辐射或拟放射性化学物质的敏感性,而对更广泛的诱变剂的敏感性被报道为低真核突变体。在所有情况下,暴露于对细胞类型过敏的物质后,对DNA合成的抑制降低。目前尚不清楚抗损伤DNA合成如何增加这些细胞的敏感性,但不太可能是导致辐射诱导细胞死亡的主要机制。对一种对辐射具有正常敏感性但仍保持耐药DNA合成的共济失调毛细血管扩张细胞系的衍生物的描述部分地将耐药DNA合成和辐射敏感性分开。本文旨在综述一些突变体中抗损伤DNA合成的现象。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Damage-resistant DNA synthesis in Eukaryotes

The molecular basis of sensitivity of ionizing radiation and other damaging agents is not clearly defined in eukaryotes. While a large number of mutants have been described only a few have been demonstrated to have a defect in the repair of damage to DNA. An interesting characteristic of a sub-group of these mutants, in different species extending throughout the phylogenetic scale, is the presence of damage-resistant DNA synthesis. This phenomenon is observed in cells from individuals with the genetic disorder ataxia telangiectasia, in HeLa cells treated with fluorodeoxyuridine prior to UV irradiation, in mutants of the fungus Neurospora crassa, the slime mould Dictyostelium discoideum, the fruit fly Drosophila melanogaster and possibly in the “wasted” mouse mutant. In the case of ataxia telangiectasia sensitivity is only observed to ionizing radiation or radiomimetic chemicals whereas sensitivity to a wider spectrum of mutagens is reported for the lower eukaryotic mutants. In all cases a reduced inhibition of DNA synthesis is obtained after exposure to an agent to which the cell type is hypersensitive. It is unclear how damage-resistant DNA synthesis contributes to increased sensitivity in these cells, but is unlikely to be the major mechanism predisposing to radiation-induced cell death. The description of a derivative of an ataxia telangiectasia cell line with normal sensitivity to radiation but still maintaining resistant DNA synthesis partially uncouples radioresistant DNA synthesis and radiosensitivity. This paper is designed to review the phenomenon of damage-resistant DNA synthesis in a number of mutants.

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