A DIRECT REPEAT IS A HOTSPOT FOR LARGE-SCALE DELETION OF HUMAN MITOCHONDRIAL-DNA
A DIRECT REPEAT IS A HOTSPOT FOR LARGE-SCALE DELETION OF HUMAN MITOCHONDRIAL-DNA
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DOI：
10.1126/science.2711184
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发表时间：
1989-04-21
期刊：
影响因子：
56.9
通讯作者：
DIMAURO, S
中科院分区：
文献类型：
--
作者：
SCHON, EA;RIZZUTO, R;DIMAURO, S
Kearns-Sayre综合征（KSS）和进行性眼外肌麻痹（PEO）是两种以眼肌病变和眼肌麻痹为特征的神经肌肉疾病。几乎所有的KSS患者和大约一半的PEO患者的线粒体基因组中都有大的缺失。这些缺失在大小和位置上都不同，除了一个5个碱基长的缺失，在超过三分之一的所有检查的患者中发现。在正常线粒体基因组中，发现这种常见的缺失侧翼有一个完美的13碱基对直接重复序列。这一结果表明，同源重组删除干预线粒体DNA的大区域，这以前只在低等真核生物和植物中观察到，在哺乳动物线粒体基因组中也起作用，并且至少是这两种相关线粒体肌病中发现的缺失的原因之一。
Kearns-Sayre syndrome (KSS) and progressive external ophthalmoplegia (PEO) are related neuromuscular disorders characterized by ocular myopathy and ophthalmoplegia. Almost all patients with KSS and about half with PEO harbor large deletions in their mitochondrial genomes. The deletions differ in both size and location, except for one, 5 kilobases long, that is found in more than one-third all all patients examined. This common deletion was found to be flanked by a perfect 13-base pair direct repeat in the normal mitochondrial genome. This result suggests that homologous recombination deleting large regions of intervening mitochondrial DNA, which previously had been observed only in lower eukaryotes and plants, operates in mammalian mitochondrial genomes as well, and is at least one cause of the deletions found in these two related mitochondrial myopathies.