title: Defects of mitochondrial DNA replication.
abstract: Mitochondrial DNA is replicated by DNA polymerase γ in concert with accessory proteins such as the mitochondrial DNA helicase, single-stranded DNA binding protein, topoisomerase, and initiating factors. Defects in mitochondrial DNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mitochondrial DNA deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mitochondrial DNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mitochondrial DNA deletion disorders, such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. This review focuses on our current knowledge of genetic defects of mitochondrial DNA replication (POLG, POLG2, C10orf2, and MGME1) that cause instability of mitochondrial DNA and mitochondrial disease.
authors.affiliation: Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA copelan1@niehs.nih.gov.
authors.forename: William C
authors.initials: WC
authors.lastname: Copeland
mesh_terms: D000818:Animals; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D028361:Mitochondrial Diseases / Q000201:enzymology / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial
keywords: Alpers syndrome; DNA polymerase γ; POLG; ataxia-neuropathy; mitochondrial DNA depletion syndrome; mitochondrial DNA replication; progressive external ophthalmoplegia