Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Mitochondrion. 2011 Nov;11(6):929-34. doi: 10.1016/j.mito.2011.08.003. Epub 2011 Aug 11.
The c.1550g→t mutation in the POLG gene causing the G517V substitution has been reported by many groups to be associated with a variety of mitochondrial diseases, including autosomal dominant and recessive forms of ataxia neuropathy, myopathy and microcephaly, progressive external ophthalmoplegia, diabetes, strokes, hypotonia, and epilepsy. However, the variable disease presentation and age of onset raises suspicion of its pathogenicity. Because of the varied reported associated symptoms and request from physicians to address the consequence of this mutation, we have carried out the biochemical analysis of the purified recombinant human DNA polymerase γ protein harboring the G517V substitution. These analyses revealed that the G517V mutant enzyme retained 80-90% of wild-type DNA polymerase activity, in addition to its functional interaction with the p55 accessory subunit. DNA binding by the mutant was also only slightly lower than the wild-type enzyme. Our data suggest that the G517V mutation by itself in pol γ most likely does not have a role in mitochondrial disorders.
许多研究小组报道，POLG 基因中的 c.1550g→t 突变导致 G517V 取代与多种线粒体疾病有关，包括常染色体显性和隐性共济失调神经病、肌病和小头症、进行性眼外肌麻痹、糖尿病、中风、张力减退和癫痫。然而，不同的疾病表现和发病年龄引起了对其致病性的怀疑。由于报告的相关症状多种多样，并且医生要求解决这种突变的后果，我们已经对携带 G517V 取代的纯化重组人 DNA 聚合酶 γ 蛋白进行了生化分析。这些分析表明，G517V 突变酶保留了 80-90%的野生型 DNA 聚合酶活性，除了与 p55 辅助亚基的功能相互作用外。突变体的 DNA 结合能力也仅略低于野生型酶。我们的数据表明，pol γ 中的 G517V 突变本身很可能在线粒体疾病中不起作用。
