The mitochondrial DNA helicase TWINKLE can assemble on a closed circular template and support initiation of DNA synthesis

Nucleic Acids Res. 2011 Nov;39(21):9238-49. doi: 10.1093/nar/gkr653. Epub 2011 Aug 12.

Abstract

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 γ. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / biosynthesis*
  • DNA Helicases / metabolism*
  • DNA Polymerase gamma
  • DNA Replication*
  • DNA, Circular / metabolism*
  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / metabolism
  • DNA-Directed DNA Polymerase / metabolism
  • Mitochondria / enzymology
  • Mitochondrial Proteins / metabolism*
  • Nucleotides / metabolism
  • Temperature
  • Templates, Genetic

Substances

  • DNA, Circular
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Mitochondrial Proteins
  • Nucleotides
  • DNA
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • DNA Helicases