The mitochondrial DNA helicase TWINKLE can assemble on a closed circular template and support initiation of DNA synthesis.
Jemt, Elisabeth 1; Farge, Geraldine 2; Backstrom, Stefan 1; Holmlund, Teresa 3; Gustafsson, Claes M. 1,4; Falkenberg, Maria 1,4,*
[Miscellaneous Article] Nucleic Acids Research. 39(21):9238-9249, November 2011.

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Mitochondrial DNA replication is performed by a simple machinery, containing the TWINKLE DNA helicase, a single-stranded DNA-binding protein, and the mitochondrial DNA polymerase [gamma]. In addition, mitochondrial RNA polymerase is required for primer formation at the origins of DNA replication. TWINKLE adopts a hexameric ring-shaped structure that must load on the closed circular mtDNA genome. In other systems, a specialized helicase loader often facilitates helicase loading. We here demonstrate that TWINKLE can function without a specialized loader. We also show that the mitochondrial replication machinery can assemble on a closed circular DNA template and efficiently elongate a DNA primer in a manner that closely resembles initiation of mtDNA synthesis in vivo.

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