title: DNA polymerase gamma and mitochondrial disease: understanding the consequence of POLG mutations.
abstract: DNA polymerase gamma is the only known DNA polymerase in human mitochondria and is essential for mitochondrial DNA replication and repair. It is well established that defects in mtDNA replication lead to mitochondrial dysfunction and disease. Over 160 coding variations in the gene encoding the catalytic subunit of DNA polymerase gamma (POLG) have been identified. Our group and others have characterized a number of the more common and interesting mutations, as well as those disease mutations in the DNA polymerase gamma accessory subunit. We review the results of these studies, which provide clues to the mechanisms leading to the disease state.
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. sherine.s.l.chan@gmail.com
authors.forename: Sherine S L
authors.initials: SS
authors.lastname: Chan
authors.forename: William C
authors.initials: WC
authors.lastname: Copeland
mesh_terms: D019943:Amino Acid Substitution; D020029:Base Pairing; D018389:Codon, Nonsense / Q000235:genetics; D017124:Conserved Sequence; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics*; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D028361:Mitochondrial Diseases / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D021122:Protein Subunits / Q000235:genetics; D014158:Transcription, Genetic; D018911:Trinucleotide Repeats
chemical_list: D018389:Codon, Nonsense; D004272:DNA, Mitochondrial; D021122:Protein Subunits; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase