POLG (alias, POLG1 or POLGa) is the gene that codes for the catalytic subunit of the mitochondrial DNA polymerase, called DNA polymerase gamma. The human POLG cDNA and gene were originally cloned mapped to chromosome 15, 15,q25. In eukaryotic cells, the mitochondrial DNA is replicated by DNA polymerase gamma, a trimeric protein complex composed of a catalytic subunit of 140kD encoded by the POLG gene and a dimeric accessory subunit of 55kD encoded by the POLG2 gene. The catalytic subunit contains three enzymatic activities, a DNA polymerase activity, a 3’-5’ exonuclease activity that proofreads misincorporated nucleotides, and a 5’-dRP lyase activity required for base excision repair. The POLG gene is also a disease locus for several mitochondrial diseases.