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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.

Authors
  • Spelbrink, J N
  • Li, F Y
  • Tiranti, V
  • Nikali, K
  • Yuan, Q P
  • Tariq, M
  • Wanrooij, S
  • Garrido, N
  • Comi, G
  • Morandi, L
  • Santoro, L
  • Toscano, A
  • Fabrizi, G M
  • Somer, H
  • Croxen, R
  • Beeson, D
  • Poulton, J
  • Suomalainen, A
  • Jacobs, H T
  • Zeviani, M
  • And 1 more
Type
Published Article
Journal
Nature genetics
Publication Date
Jul 01, 2001
Volume
28
Issue
3
Pages
223–231
Identifiers
PMID: 11431692
Source
Medline
License
Unknown

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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