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DNA双链断裂:其在酵母中的修复及与细胞杀伤的关系

DNA double-strand breaks: their repair and relationship to cell killing in yeast.

作者信息

Frankenberg-Schwager M, Frankenberg D

机构信息

Gesellschaft für Strahlen- und Umweltforschung mbH, Institut für Biophys. Strahlenforschung, Frankfurt, FRG.

出版信息

Int J Radiat Biol. 1990 Oct;58(4):569-75. doi: 10.1080/09553009014551931.

DOI:10.1080/09553009014551931
PMID:1976718
Abstract

Yeast is a suitable eukaryotic organism in which to study DNA double-strand breakage measured by the neutral sucrose gradient sedimentation technique and cell killing in the same range dose of sparsely ionizing radiations. Radiosensitive mutants (including temperature conditional ones) exist in which rejoining of double-strand breaks (dsb) is not detectable. In such mutants approximately one dsb per cell corresponds to a lethal event, suggesting that a dsb is a potentially lethal lesion. There are two modes by which dsb may confer cell lethality: firstly, an unrepaired dsb may be lethal on its own and secondly, two dsb may interact to form a lethal lesion (binary misrepair). The operationally defined cellular phenomena of potentially lethal damage (PLD) repair and sublethal damage (SLD) repair are both based on the repair of dsb. Induced dsb show a linear and unrejoined dsb a linear-quadratic relationship with dose. At low dose rate the quadratic component is abolished in accordance with the exponential survival curve observed. The dose-rate effect is based on dsb repair during irradiation; it is absent in dsb repair-deficient mutants.

摘要

酵母是一种合适的真核生物,可用于研究通过中性蔗糖梯度沉降技术测量的DNA双链断裂以及在相同剂量范围内的低线性能量传递辐射的细胞杀伤作用。存在放射敏感突变体(包括温度条件突变体),在这些突变体中无法检测到双链断裂(dsb)的重新连接。在这种突变体中,每个细胞大约一个dsb对应一个致死事件,这表明dsb是一种潜在的致死性损伤。dsb导致细胞致死有两种方式:首先,未修复的dsb本身可能是致死的;其次,两个dsb可能相互作用形成致死性损伤(二元错配修复)。潜在致死性损伤(PLD)修复和亚致死性损伤(SLD)修复这两种在操作上定义的细胞现象均基于dsb的修复。诱导的dsb与剂量呈线性关系,未重新连接的dsb与剂量呈线性二次关系。在低剂量率下,根据观察到的指数存活曲线,二次成分消失。剂量率效应基于辐照期间的dsb修复;在dsb修复缺陷的突变体中不存在这种效应。

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