title: In vivo mutagenesis reveals that OriL is essential for mitochondrial DNA replication.
abstract: The mechanisms of mitochondrial DNA replication have been hotly debated for a decade. The strand-displacement model states that lagging-strand DNA synthesis is initiated from the origin of light-strand DNA replication (OriL), whereas the strand-coupled model implies that OriL is dispensable. Mammalian mitochondria cannot be transfected and the requirements of OriL in vivo have therefore not been addressed. We here use in vivo saturation mutagenesis to demonstrate that OriL is essential for mtDNA maintenance in the mouse. Biochemical and bioinformatic analyses show that OriL is functionally conserved in vertebrates. Our findings strongly support the strand-displacement model for mtDNA replication.
authors.affiliation: Department of Medical Biochemistry and Cell Biology, University of Gothenburg, P.O. Box 440, SE-405 30 Gothenburg, Sweden.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Wanrooij
authors.forename: Javier
authors.initials: J
authors.lastname: Miralles Fusté
authors.forename: James B
authors.initials: JB
authors.lastname: Stewart
authors.forename: Paulina H
authors.initials: PH
authors.lastname: Wanrooij
authors.forename: Tore
authors.initials: T
authors.lastname: Samuelsson
authors.forename: Nils-Göran
authors.initials: NG
authors.lastname: Larsson
authors.forename: Claes M
authors.initials: CM
authors.lastname: Gustafsson
authors.forename: Maria
authors.initials: M
authors.lastname: Falkenberg
mesh_terms: D000818:Animals; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D016296:Mutagenesis; D010802:Phylogeny; D018741:Replication Origin / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D004247:DNA; C513299:Twnk protein, mouse; D004265:DNA Helicases