title: Replication stalling by catalytically impaired Twinkle induces mitochondrial DNA rearrangements in cultured cells.
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.
authors.affiliation: Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany. Jaakko.Pohjoismaeki@mpi-bn.mpg.de
authors.forename: Jaakko L O
authors.initials: JL
authors.lastname: Pohjoismäki
authors.forename: Steffi
authors.initials: S
authors.lastname: Goffart
authors.forename: Johannes N
authors.initials: JN
authors.lastname: Spelbrink
mesh_terms: D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression; D015321:Gene Rearrangement; D054629:Genome, Mitochondrial; D057809:HEK293 Cells; D006801:Humans; D046529:Microscopy, Electron, Transmission; D024101:Mitochondrial Proteins; D009154:Mutation
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D004265:DNA Helicases; C431576:TWNK protein, human