DNA polymerase gamma and mitochondrial disease: understanding the consequence of POLG mutations

Biochim Biophys Acta. 2009 May;1787(5):312-9. doi: 10.1016/j.bbabio.2008.10.007. Epub 2008 Oct 29.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Amino Acid Substitution
  • Base Pairing
  • Codon, Nonsense / genetics
  • Conserved Sequence
  • DNA Polymerase gamma
  • DNA, Mitochondrial / genetics*
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / genetics*
  • Diffuse Cerebral Sclerosis of Schilder / genetics
  • Genetic Variation
  • Humans
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Mitochondrial Diseases / genetics*
  • Models, Molecular
  • Mutation*
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Protein Conformation
  • Protein Subunits / genetics
  • Transcription, Genetic
  • Trinucleotide Repeats


  • Codon, Nonsense
  • DNA, Mitochondrial
  • Protein Subunits
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase