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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mitochondrial mutational spectra in human cells and tissues
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Mitochondrial mutational spectra in human cells and tissues

机译:人类细胞和组织中的线粒体突变谱

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摘要

We have found that human organs such as colon, lung, and muscle, as well as their derived tumors, share nearly all mitochondrial hotspot point mutations. Seventeen hotspots, primarily G - A and A - G transitions, have been identified in the mitochondrial sequence of base pairs 10,030- 10,130. Mutant fractions increase with the number of cell generations in a human B cell line, TK6, indicating that they are heritable changes. The mitochondrial point mutation rate appears to be more than two orders of magnitude higher than the nuclear point mutation rate in TK6 cells and in human tissues. The similarity of the hotspot sets in vivo and in vitro leads us to conclude that human mitochondrial point muta- tions in the sequence studied are primarily spontaneous in origin and arise either from DNA replication error or reac- tions of DNA with endogenous metabolites.
机译:我们发现,人体器官(例如结肠,肺和肌肉)及其衍生的肿瘤几乎共享所有线粒体热点点突变。在碱基对10,030-10,130的线粒体序列中已识别出17个热点,主要是G-A和A-G跃迁。突变分数随人B细胞系TK6中细胞世代数的增加而增加,表明它们是可遗传的变化。线粒体点突变率似乎比TK6细胞和人体组织中的核点突变率高两个数量级。体内和体外热点集的相似性使我们得出结论,即所研究序列中的人线粒体点突变主要是自发的,并且可能是由于DNA复制错误或DNA与内源性代谢物的反应所致。

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