CROSS-SENSITIVITY OF GAMMA-RAY-SENSITIVE HAMSTER MUTANTS TO CROSS-LINKING AGENTS
CROSS-SENSITIVITY OF GAMMA-RAY-SENSITIVE HAMSTER MUTANTS TO CROSS-LINKING AGENTS
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DOI：
10.1016/0921-8777(91)90046-r
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发表时间：
1991-09-01
期刊：
影响因子：
--
通讯作者：
JEGGO, P
中科院分区：
文献类型：
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作者：
CALDECOTT, K;JEGGO, P
研究人员检测了一系列对电离辐射敏感的仓鼠细胞突变体对四种DNA-DNA交联剂和蛋白质-DNA交联剂喜树碱的交叉敏感性。突变体代表7个不同的互补组。两个互补基团被鉴定为对交联损伤具有主要敏感性，比它们对电离辐射(IRS1，irs1SF)的敏感性更明显。这两个突变体也表现出对紫外线的敏感性。剩下的两个互补基团(XRS和XR-1)在重新连接DNA双链断裂方面存在缺陷，这些基团对4种DNA-DNA交联剂中的3种表现出敏感性。对这些突变体的结果表明，双链断裂重新连接参与了某些交联链损伤的修复。两个突变体对抑制拓扑异构酶I的抗癌药物喜树碱也非常敏感。其中一个突变株对所检测的DNA交联剂(Irs1SF)敏感，而另一个突变株对这种药物(EM9)完全不敏感。
A range of hamster cell mutants, which have been characterised as sensitive to ionising radiation, were examined for their cross-sensitivity to four DNA-DNA cross-linking agents and the protein-DNA cross-linking agent, camptothecin. The mutants represent 7 distinct complementation groups. Two complementation groups were identified as having a major sensitivity to cross-linking damage, more marked than their sensitivity to ionising radiation (irs1, irs1SF). These two mutants also show sensitivity to UV-irradiation. Two of the remaining complementation groups (xrs and XR-1) have a defect in rejoining DNA double-strand breaks, and these exhibit sensitivity to 3 of the 4 DNA-DNA cross-linking agents. The results with these mutants suggest an involvement of double-strand break rejoining in the repair of certain cross-link damage. Two mutants were also notably sensitive to the topoisomerase I inhibiting anticancer drug, camptothecin. One of these mutants was sensitive to the DNA cross-linking agents examined (irs1SF), but the other was not at all sensitive to this class of drug (EM9).