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Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria.
- Source :
-
Nature genetics [Nat Genet] 2001 Jul; Vol. 28 (3), pp. 223-31. - Publication Year :
- 2001
-
Abstract
- 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 cluster 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.
- Subjects :
- Amino Acid Sequence
Cell Compartmentation
Chromosomes, Human, Pair 10 genetics
DNA Helicases
Female
Finland epidemiology
Genetic Linkage
Heterozygote
Humans
Italy epidemiology
Male
Mitochondrial Proteins
Molecular Sequence Data
Ophthalmoplegia, Chronic Progressive External epidemiology
Pakistan epidemiology
Pedigree
Protein Conformation
Protein Transport
Sequence Homology, Amino Acid
DNA Primase genetics
DNA, Mitochondrial genetics
Mutation genetics
Ophthalmoplegia, Chronic Progressive External genetics
Sequence Deletion
Subjects
Details
- Language :
- English
- ISSN :
- 1061-4036
- Volume :
- 28
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 11431692
- Full Text :
- https://doi.org/10.1038/90058