Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria.
Nat Genet
; 28(3): 223-31, 2001 Jul.
Article
em En
| MEDLINE
| ID: mdl-11431692
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Mitocondrial
/
Deleção de Sequência
/
Oftalmoplegia Externa Progressiva Crônica
/
DNA Primase
/
Mutação
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
País/Região como assunto:
Asia
/
Europa
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Finlândia