DNA polymerase subunit gamma, catalytic subunit (POLG)

DNA polymerase subunit gamma, catalytic subunit (POLG), is the primary enzyme responsible for replicating and repairing mitochondrial DNA in human cells. This large mitochondrial enzyme functions as the catalytic α (alpha) subunit of the heterotrimeric DNA polymerase gamma holoenzyme, which also includes a dimeric accessory β (beta) subunit that increases processivity and DNA binding. POLG exhibits polymerase activity for DNA synthesis, 3'-5' exonuclease activity for proofreading, and 5'-deoxyribose-phosphate lyase activity for base excision repair. Mutations in POLG are associated with a spectrum of mitochondrial diseases characterized by impaired energy metabolism, neurodegeneration, hepatopathy, and myopathy. Off-target inhibition or mutation of POLG can cause or exacerbate mitochondrial toxicities, especially in the context of certain drugs such as valproic acid or some nucleoside analogs, making POLG both a clinically significant disease gene and an important safety consideration in drug development.

Other names

DNA polymerase gamma catalytic subunitDNA polymerase gamma-1POLG1POLGAMDP13'-5' exodeoxyribonuclease5'-deoxyribose-phosphate lyasemitochondrial DNA polymerase catalytic subunitPolG-alphaMIRASMTDPS4AMTDPS4BPEOSANDOSCAEDNA polymerase subunit gamma-1

Inhibition (by off-target drug effects leading to mitochondrial dysfunction); Mutation rescue (small molecules restoring mutant POLG function)