Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene LF-like protein localized in mitochondria
Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene LF-like protein localized in mitochondria
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DOI：
10.1038/90058
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发表时间：
2001-07-01
期刊：
影响因子：
30.8
通讯作者：
Larsson, C
中科院分区：
文献类型：
--
作者：
Spelbrink, JN;Li, FY;Larsson, C
参与哺乳动物线粒体DNA（mtDNA）维持和组织的基因产物在很大程度上仍然未知。我们在这里报告一个新的线粒体蛋白。闪烁，与噬菌体T7基因4引发酶/解旋酶和其他六聚环解旋酶具有结构相似性。Twinkle在线粒体类核中与mtDNA共定位。常染色体显性进行性眼外肌麻痹（adPEO）个体中编码Twinkle的基因的筛选。与多个mtDNA缺失相关，在12个不同种族来源的adPEO家系中鉴定出与该疾病共分离的11个不同编码区突变。这些突变集中在蛋白质的一个区域，被认为与亚基相互作用有关。Twinkle的功能被推断为对人类mtDNA完整性的终身维持至关重要。
The gene products involved in mammalian mitochondrial DNA (mtDNA) maintenance and organization remain largely unknown. We report here a novel mitochondrial protein. Twinkle, with structural similarity to phage T7 gene 4 primase/helicase and other hexameric ring helicases. Twinkle colocalizes with mtDNA in mitochondrial nucleoids. Screening of the gene encoding Twinkle in individuals with autosomal dominant progressive external ophthalmoplegia (adPEO). associated with multiple mtDNA deletions, identified 11 different coding-region mutations co-segregating with the disorder in 12 adPEO pedigrees of various ethnic origins. The mutations duster in a region of the protein proposed to be involved in subunit interactions. The function of Twinkle is inferred to be critical for lifetime maintenance of human mtDNA integrity.