非表示:
キーワード:
Animals
Conserved Sequence
DNA/genetics
DNA Helicases/genetics/metabolism
DNA Replication/*genetics
*DNA, Mitochondrial/biosynthesis/genetics
Humans
Mice
Mitochondria/genetics
Mitochondrial Proteins/genetics/metabolism
Models, Genetic
*Mutagenesis
Phylogeny
Replication Origin/*genetics
Sequence Analysis, DNA
要旨:
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.