Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria

Johannes N. Spelbrink, Fang Yuan Li, Valeria Tiranti, Kaisu Nikali, Qiu Ping Yuan, Muhammed Tariq, Sjoerd Wanrooij, Nuria Garrido, Giacomo Comi, Lucia Morandi, Lucio Santoro, Antonio Toscano, Gian Maria Fabrizi, Hannu Somer, Rebecca Croxen, David Beeson, Joanna Poulton, Anu Suomalainen, Howard T. Jacobs, Massimo Zeviani & 1 others Catharina Larsson

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)223-231
Number of pages9
JournalNature Genetics
Volume28
Issue number3
DOIs
Publication statusPublished - 2001

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DNA Primase
Bacteriophage T7
Mitochondrial DNA
Mitochondria
Chronic Progressive External Ophthalmoplegia
Mutation
Genes
Mitochondrial Proteins
Pedigree
Maintenance
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. / Spelbrink, Johannes N.; Li, Fang Yuan; Tiranti, Valeria; Nikali, Kaisu; Yuan, Qiu Ping; Tariq, Muhammed; Wanrooij, Sjoerd; Garrido, Nuria; Comi, Giacomo; Morandi, Lucia; Santoro, Lucio; Toscano, Antonio; Fabrizi, Gian Maria; Somer, Hannu; Croxen, Rebecca; Beeson, David; Poulton, Joanna; Suomalainen, Anu; Jacobs, Howard T.; Zeviani, Massimo; Larsson, Catharina.

In: Nature Genetics, Vol. 28, No. 3, 2001, p. 223-231.

Research output: Contribution to journalArticle

Spelbrink, JN, Li, FY, Tiranti, V, Nikali, K, Yuan, QP, Tariq, M, Wanrooij, S, Garrido, N, Comi, G, Morandi, L, Santoro, L, Toscano, A, Fabrizi, GM, Somer, H, Croxen, R, Beeson, D, Poulton, J, Suomalainen, A, Jacobs, HT, Zeviani, M & Larsson, C 2001, 'Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria', Nature Genetics, vol. 28, no. 3, pp. 223-231. https://doi.org/10.1038/90058
Spelbrink, Johannes N. ; Li, Fang Yuan ; Tiranti, Valeria ; Nikali, Kaisu ; Yuan, Qiu Ping ; Tariq, Muhammed ; Wanrooij, Sjoerd ; Garrido, Nuria ; Comi, Giacomo ; Morandi, Lucia ; Santoro, Lucio ; Toscano, Antonio ; Fabrizi, Gian Maria ; Somer, Hannu ; Croxen, Rebecca ; Beeson, David ; Poulton, Joanna ; Suomalainen, Anu ; Jacobs, Howard T. ; Zeviani, Massimo ; Larsson, Catharina. / Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. In: Nature Genetics. 2001 ; Vol. 28, No. 3. pp. 223-231.
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