title: Consequences of mutations in human DNA polymerase gamma.
abstract: DNA polymerase gamma is responsible for replication and repair of the mitochondrial genome. Human DNA polymerase gamma is composed of a 140-kDa catalytic subunit and a 55-kDa accessory subunit. Mutations in the gene for the catalytic subunit (POLG) have been shown to be a frequent cause of mitochondrial disorders. To date over 40 disease mutations and 9 nonsynonymous polymorphisms in POLG have been found to be associated with autosomal recessive and dominant progressive external ophthalmoplegia (PEO), Alpers syndrome, sensory ataxia, neuropathy, dysarthria and ophthalmoparesis (SANDO), Parkinsonism, and male infertility. In this paper we review the literature of POLG mutations and discuss their impact on mitochondrial diseases. We also describe a public access web database to annotate POLG mutations for the research community.
authors.affiliation: Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Research Triangle Park, NC 27709, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Longley
authors.forename: Maria A
authors.initials: MA
authors.lastname: Graziewicz
authors.forename: Rachelle J
authors.initials: RJ
authors.lastname: Bienstock
authors.forename: William C
authors.initials: WC
authors.lastname: Copeland
mesh_terms: D000595:Amino Acid Sequence; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics*; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009886:Ophthalmoplegia / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation
chemical_list: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase