DNA polymerase alpha, DNA polymerase delta, and DNA polymerase epsilon (Pol α (alpha), Pol δ (delta), Pol ε (epsilon))

DNA polymerase alpha, delta, and epsilon are three essential B-family enzymes responsible for the faithful replication of nuclear DNA in eukaryotic cells. DNA polymerase alpha initiates DNA replication by extending RNA primers with short stretches of DNA, after which DNA polymerase delta (primarily lagging strand synthesis) and DNA polymerase epsilon (primarily leading strand synthesis) take over to elongate the majority of the genome[3][7][9]. All three enzymes are multi-subunit complexes with distinct catalytic and regulatory subunits necessary for their function and regulation[5][9]. They play critical roles in cell cycle progression, genome maintenance, and various DNA repair pathways[2][3][6]. Mutations in their genes—particularly those affecting proofreading domains of delta and epsilon—are associated with increased risk of cancer and other diseases due to elevated mutagenesis[3][9]. Several anticancer drugs and experimental inhibitors act by targeting their activity, but the essential nature of these enzymes in healthy proliferating tissues creates therapeutic challenges concerning toxicity[9].

Other names

Pol α, Pol δ, Pol εFamily B DNA polymerases

Inhibition of DNA polymerase activity, leading to impaired DNA replication and cell cycle arrest - Induction of replication stress, DNA damage, or apoptosis in rapidly dividing cells