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In vivo mutagenesis reveals that OriL is essential for mitochondrial DNA replication
Author(s) -
Wanrooij Sjoerd,
Miralles Fusté Javier,
Stewart James B,
Wanrooij Paulina H,
Samuelsson Tore,
Larsson NilsGöran,
Gustafsson Claes M,
Falkenberg Maria
Publication year - 2012
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2012.161
Subject(s) - biology , dna replication , mitochondrial dna , genetics , mutagenesis , control of chromosome duplication , dna , microbiology and biotechnology , eukaryotic dna replication , mutation , gene
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.