DNA polymerase subunit gamma-1 (POLG) (POLG)

Human mitochondrial DNA polymerase gamma (POLG) is the primary enzyme responsible for the replication and repair of mitochondrial DNA (mtDNA) (UniProt: P54098). It is a heterotrimeric complex consisting of a catalytic subunit (POLG1) and a dimeric accessory subunit (POLG2) (PubMed: 28235861). POLG possesses DNA polymerase activity, 3'-5' exonuclease activity for proofreading, and 5'-deoxyribose phosphate lyase activity for base excision repair (NCBI Gene: 5428). Mutations in the POLG gene are a major cause of mitochondrial diseases, ranging from early-onset Alpers-Huttenlocher syndrome to adult-onset progressive external ophthalmoplegia (PubMed: 30243044). In pharmacology, POLG is a critical off-target for nucleoside reverse transcriptase inhibitors (NRTIs) used in HIV treatment; inhibition of POLG by these drugs leads to mtDNA depletion and clinical toxicities such as lactic acidosis and lipodystrophy (PubMed: 11518513). Understanding POLG function is essential for assessing the safety profile of antiviral drugs and for diagnosing a wide spectrum of mitochondrial genetic disorders.

Other names

POLG1Mitochondrial DNA polymerasePolymerase (DNA) gammaPEOA1POLG

Inhibition of mitochondrial DNA polymerase activity leading to depletion of mitochondrial DNA and mitochondrial dysfunction (PubMed: 11518513).