DNA polymerase subunit gamma-1 (POLG)

DNA polymerase subunit gamma-1 (POLG) is the catalytic subunit of mitochondrial DNA polymerase gamma, the sole DNA polymerase responsible for replication and repair of mitochondrial DNA in human cells. It forms the holoenzyme as a heterotrimer, composed of one POLG catalytic subunit and a homodimer of accessory (beta) subunits, which together ensure efficient and accurate replication of the mitochondrial genome. Mutations in POLG are directly associated with a broad range of mitochondrial diseases, particularly affecting tissues highly dependent on oxidative phosphorylation, such as the brain, muscle, and liver. POLG is also susceptible to inhibition by some antiviral drugs, leading to off-target mitochondrial toxicity. It is a key enzyme in mitochondrial genome maintenance, with both DNA polymerase and 3′–5′ exonuclease (proofreading) activities.

Other names

DNA polymerase gamma catalytic subunitPolymerase (DNA directed), gammaPolymerase (DNA) gamma, catalytic subunitMitochondrial DNA polymerase catalytic subunitPolG, catalytic subunitPolG-alphaPOLG1POLGA

Inhibition of polymerase activity, leading to impaired mitochondrial DNA replication and depletion (for drugs that target both HIV reverse transcriptase and inadvertently inhibit POLG)