title: Human mitochondrial DNA replication machinery and disease.
abstract: The human mitochondrial genome is replicated by DNA polymerase γ in concert with key components of the mitochondrial DNA (mtDNA) replication machinery. Defects in mtDNA replication or nucleotide metabolism cause deletions, point mutations, or depletion of mtDNA. The resulting loss of cellular respiration ultimately induces mitochondrial genetic diseases, including mtDNA depletion syndromes (MDS) such as Alpers or early infantile hepatocerebral syndromes, and mtDNA deletion disorders such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. Here we review the current literature regarding human mtDNA replication and heritable disorders caused by genetic changes of the POLG, POLG2, Twinkle, RNASEH1, DNA2, and MGME1 genes.
authors.affiliation: Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, United States.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Young
authors.affiliation: Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, United States. Electronic address: copelan1@niehs.nih.gov.
authors.forename: William C
authors.initials: WC
authors.lastname: Copeland
mesh_terms: D019069:Cell Respiration / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D000074002:DNA Polymerase gamma; D004261:DNA Replication / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics; D054629:Genome, Mitochondrial; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation; D016914:Ribonuclease H / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; C544932:POLG2 protein, human; D005090:Exodeoxyribonucleases; C579164:MGME1 protein, human; D016914:Ribonuclease H; C078856:ribonuclease HI; D004265:DNA Helicases; C509908:DNA2 protein, human; C431576:TWNK protein, human