Replication stalling by catalytically impaired Twinkle induces mitochondrial DNA rearrangements in cultured cells

Mitochondrion. 2011 Jul;11(4):630-4. doi: 10.1016/j.mito.2011.04.002. Epub 2011 Apr 20.

Abstract

Pathological mitochondrial DNA (mtDNA) rearrangements have been proposed to result from repair of double-strand breaks caused by blockage of mitochondrial DNA (mtDNA) replication. As mtDNA deletions are seen only in post-mitotic tissues, it has been suggested that they are selected out in actively dividing cells. By electron microscopy we observed rearranged mtDNA molecules in cultured human cells expressing a catalytically impaired helicase. As these molecules were undetectable by PCR, we propose that deleted mtDNA molecules in cultured cells are fragile and sensitive to heating. Further consequences of mtDNA replication stalling are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Breaks, Double-Stranded
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Replication*
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • DNA, Mitochondrial / ultrastructure
  • Gene Expression
  • Gene Rearrangement
  • Genome, Mitochondrial
  • HEK293 Cells
  • Humans
  • Microscopy, Electron, Transmission
  • Mitochondrial Proteins
  • Mutation

Substances

  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • DNA Helicases
  • TWNK protein, human