The formation, identification, and significance of DNA-protein cross-links in mammalian cells.
The formation, identification, and significance of DNA-protein cross-links in mammalian cells.
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发表时间：
1987-06
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通讯作者：
N. Oleinick;S. Chiu;Narayani Ramakrishnan;L. Xue
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作者：
N. Oleinick;S. Chiu;Narayani Ramakrishnan;L. Xue
DNA-蛋白质交联物(DPC)是由各种辐射和化学物质通过自由基形成而形成的。共价性是从交联体对严酷处理的抗性推断出来的。在哺乳动物细胞中，DPC的背景(每V79细胞6000个)可能是染色体环与核蛋白基质的正常结合造成的。在电离辐射后，升高的DPC水平(每GyV79细胞150)被活跃地转录DNA和核基质的一部分蛋白质所富含。DPC的形成被羟基自由基清除剂、氧气和高渗介质减少，而通过低渗介质和细胞内谷胱甘肽的去除而增强。DPC的修复速度比单链断裂慢，而且在中期形成时根本不修复。在辐射后阶段，残留DPC的DNA序列组成的变化与活跃表达基因中DPC的优先修复是一致的。切除修复机制已被提出。未修复的DPC可能会阻碍核基质的正常功能，如复制和转录。
DNA-protein cross-links (DPC) are formed by a variety of radiations and chemicals which act via free radical formation. Covalency is inferred from the resistance of the cross-links to harsh treatments. In mammalian cells, a background of DPC (6000 per V79 cell) may result from normal associations of chromosomal loops with the nuclear protein matrix. After ionizing radiation, the elevated level of DPC (150 per Gy per V79 cell) are enriched in actively transcribing DNA and in a subset of proteins of the nuclear matrix. DPC formation is reduced by hydroxyl radical scavengers, by oxygen, and by hypertonic medium and is enhanced by hypotonic medium and by removal of intracellular glutathione. DPC are repaired more slowly than single-strand breaks and not at all when formed during metaphase. During the postirradiation period, changes in the sequence composition of the DNA of residual DPC are consistent with the preferential repair of DPC in actively expressed genes. Excision repair mechanisms have been proposed. Unrepaired DPC may block normal functions of the nuclear matrix, such as replication and transcription.