Abstract
The field of mitochondrial DNA (mtDNA) replication has been experiencing incredible progress in recent years, and yet little is certain about the mechanism(s) used by animal cells to replicate this plasmid-like genome. The long-standing strand-displacement model of mammalian mtDNA replication (for which single-stranded DNA intermediates are a hallmark) has been intensively challenged by a new set of data, which suggests that replication proceeds via coupled leading- and lagging-strand synthesis (resembling bacterial genome replication) and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand (the so called RITOLS). The set of proteins required for mtDNA replication is small and includes the catalytic and accessory subunits of DNA polymerase γ, the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding protein, and the mitochondrial RNA polymerase (which most likely functions as the mtDNA primase). Mutations in the genes coding for the first three proteins are associated with human diseases and premature aging, justifying the research interest in the genetic, biochemical and structural properties of the mtDNA replication machinery. Here we summarize these properties and discuss the current models of mtDNA replication in animal cells.
Highlights
The mitochondrial genome was thought to be a less important plasmid-like DNA, which contained residual genetic information from the ancestral a-proteobacterium that eventually became the mitochondrion, determining one of the most important endosymbiotic events in the evolutionary history of eukaryotes
We focus on the recent discoveries in mitochondrial DNA (mtDNA) replication in animal cells
Researchers in the last two decades have studied the subject on two fronts: 1) investigating the composition of mtDNA replication intermediates in vivo and in cells in culture; and 2) investigating the biochemical and physical properties of the proteins involved in mtDNA maintenance
Summary
The mitochondrial genome was thought to be a less important plasmid-like DNA, which contained residual genetic information from the ancestral a-proteobacterium that eventually became the mitochondrion, determining one of the most important endosymbiotic events in the evolutionary history of eukaryotes. These studies have shown that the mtDNA transactions are more diverse and complex than previously thought (for more details on these transactions, see Oliveira et al, 2010), revealing new mechanisms of genome replication with implications for the understanding of human mitochondrial disorders and the evolution of animal mitochondria.
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