ERRORS IN DNA-SYNTHESIS - A SOURCE OF SPONTANEOUS MUTATIONS
ERRORS IN DNA-SYNTHESIS - A SOURCE OF SPONTANEOUS MUTATIONS
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DOI：
10.1016/0165-1110(90)90021-3
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发表时间：
1990-05-01
期刊：
影响因子：
--
通讯作者：
CHENG, KC
中科院分区：
文献类型：
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作者：
LOEB, LA;CHENG, KC
体细胞中的自发突变可引起几种病理过程，包括癌症。这些突变的来源仍有待确定。我们提出了一个概念框架，在其中分析自发突变的来源，并在这里集中在3个内源性的过程，有可能产生自发的DNA序列改变。这些是：复制错误，脱嘌呤的DNA，和损伤的DNA的活性氧的产生。这些过程中的每一个都比体细胞中的诱变速率更频繁地发生，但通过不同和重叠的机制进行修复。正在开发模型系统，以确定由这些过程中的每一个在体外产生的突变谱。将这些光谱与体细胞中自发突变的总体光谱进行比较，可能有助于确定这些过程中的每一个对自发突变的贡献。
Spontaneous mutations in somatic cells may engender several pathologic processes, including cancer. The sources of these mutations remain to be established. We present a conceptual framework in which to analyze the sources of spontaneous mutations and focus here on 3 endogenous processes that have the potential to generate spontaneous sequence alterations in DNA. These are: replication errors, depurination of DNA, and damage to DNA by the generation of active-oxygen species. Each of these processes occurs more frequently than the rate of mutagenesis in somatic cells, but are repaired by different and overlapping mechanisms. Model systems are being developed to determine the spectrum of mutations produced by each of these processes in vitro. A comparison of these spectra with the overall spectrum of spontaneous mutations in somatic cells may help to determine the contribution of each of these processes to spontaneous mutation.