Behaviour of a population of partially duplicated mitochondrial DNA molecules in cell culture: Segregation, maintenance and recombination dependent upon nuclear background
Behaviour of a population of partially duplicated mitochondrial DNA molecules in cell culture: Segregation, maintenance and recombination dependent upon nuclear background
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DOI：
10.1093/hmg/6.8.1251
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发表时间：
1997-08-01
影响因子：
3.5
通讯作者：
Jacobs, HT
中科院分区：
文献类型：
--
作者：
Holt, IJ;Dunbar, DR;Jacobs, HT
我们已经研究了线粒体DNA的维护和分离在人类细胞中使用的部分复制的线粒体DNA，从线粒体肌病患者，到两个不同的受体细胞类型的连续胞质杂交转移的动力学。结果表明，两个根本不同的结果取决于核背景。在一种情况下（肺癌），有一个隐含的重组机制的部分重复的系统性损失。在另一种核背景（骨肉瘤）中，复制的分子可以存活，对线粒体呼吸功能只有轻微的影响。此外，在骨肉瘤细胞核背景中，线粒体DNA维持的进一步紊乱经常伴随着胞质杂种转移。这些是线粒体DNA的渐进性、灾难性丢失和进一步重排，以产生部分三重分子。这些结果表明，在不同的人类细胞类型中，调节mtDNA拷贝数、复制和重组的核基因的表达存在差异。
We have studied the dynamics of mitochondrial DNA maintenance and segregation in human cells using serial cybrid transfer of partially duplicated mitochondrial DNA, from a mitochondrial myopathy patient, to two distinct recipient cell types. The results indicate two radically different outcomes dependent upon nuclear background. In one case (lung carcinoma) there is systematic loss of the partial duplication by an implied recombinational mechanism. In another nuclear background (osteosarcoma) the duplicated molecules can survive, having only a marginal effect on mitochondrial respiratory function. Moreover, in the osteosarcoma nuclear background further disturbances of mtDNA maintenance frequently follow from cybrid transfer. These are progressive, catastrophic loss of mtDNA and further rearrangement to generate partially triplicated molecules. The results imply differential expression of nuclear genes regulating mtDNA copy number, replication and recombination in different human cell types.