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

TitleHuman mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria.
Publication TypeJournal Article
Year of Publication2001
AuthorsSpelbrink, 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
JournalNat Genet
Volume28
Issue3
Pagination223-31
Date Published2001 Jul
ISSN1061-4036
KeywordsAmino Acid Sequence, Cell Compartmentation, Chromosomes, Human, Pair 10, DNA Helicases, DNA Primase, DNA, Mitochondrial, Female, Finland, Genetic Linkage, Heterozygote, Humans, Italy, Male, Mitochondrial Proteins, Molecular Sequence Data, Mutation, Ophthalmoplegia, Chronic Progressive External, Pakistan, Pedigree, Protein Conformation, Protein Transport, Sequence Deletion, Sequence Homology, Amino Acid
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.

DOI10.1038/90058
Alternate JournalNat. Genet.
Citation Key10.1038/90058
PubMed ID11431692
Grant List1180 / / Telethon / Italy