InterPro domain: IPR027032

Twinkle protein (T7-like mitochondrial DNA helicase) is a DNA helicase needed for mitochondrial DNA replication [ 1 ]. It catalyses the ATP-dependent unwinding of a DNA duplex with 5' to 3' directionality, and it needs a single-stranded 5'-DNA and a short 3'-tail to initiate unwinding [ 2 ]. In humans, mutations in TWINKLE cause autosomal dominant progressive external ophthalmoplegia, a human disorder associated with multiple deletions in the mitochondrial DNA [ 3 ]. Arabidopsis encodes a homologue to phage T7 gp4/Twinkle proteins that has both DNA primase and DNA helicase activities [ 4 ].

1. Structure-function defects of the twinkle amino-terminal region in progressive external ophthalmoplegia. Biochim. Biophys. Acta 1792, 132-9
2. TWINKLE Has 5' -> 3' DNA helicase activity and is specifically stimulated by mitochondrial single-stranded DNA-binding protein. J. Biol. Chem. 278, 48627-32
3. 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, 223-31
4. The Arabidopsis At1g30680 gene encodes a homologue to the phage T7 gp4 protein that has both DNA primase and DNA helicase activities. BMC Plant Biol. 13, 36