Human DNA polymerases alpha, beta, and mitochondrial gamma (Pol α, Pol β, Pol γ)

Human DNA polymerases alpha (Pol α), beta (Pol β), and mitochondrial gamma (Pol γ) are essential enzymes responsible for the synthesis and maintenance of nuclear and mitochondrial genomes. Pol α is a member of the B-family polymerases and is critical for the initiation of nuclear DNA replication by synthesizing RNA-DNA primers (UniProt P09884). Pol β belongs to the X-family and serves as a primary enzyme in the base excision repair (BER) pathway, maintaining genomic integrity by filling small gaps in DNA (UniProt P06746). Pol γ is the sole polymerase found in human mitochondria, belonging to the A-family, and is responsible for the replication and repair of mitochondrial DNA (mtDNA) (UniProt P54098). These enzymes are significant in pharmacology as both primary targets and sources of off-target toxicity. For instance, certain nucleoside analog reverse transcriptase inhibitors (NRTIs) used in HIV treatment can inadvertently inhibit Pol γ, leading to mitochondrial depletion and clinical side effects such as lactic acidosis and peripheral neuropathy (PubMed: 11133337). Conversely, inhibitors of replicative polymerases like Pol α, such as cytarabine, are utilized in cancer chemotherapy to arrest cell proliferation (PubMed: 16406223).

Other names

DNA polymerase alphaDNA polymerase betaDNA polymerase gammaPOLA1POLBPOLGDNA-directed DNA polymerase alphaDNA-directed DNA polymerase betaDNA-directed DNA polymerase gamma

Competitive inhibition of dNTP binding and DNA chain termination following incorporation into the nascent DNA strand.