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
in 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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA, Mitochondrial
/
Sequence Deletion
/
Ophthalmoplegia, Chronic Progressive External
/
DNA Primase
/
Mutation
Type of study:
Risk_factors_studies
Limits:
Female
/
Humans
/
Male
Country/Region as subject:
Asia
/
Europa
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2001
Type:
Article
Affiliation country:
Finland