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DNA polymerase alpha-associated DNA primase (Pol α-primase) is a multi-subunit enzyme complex essential for the initiation of eukaryotic DNA replication. It consists of the catalytic and regulatory subunits of DNA polymerase alpha (POLA1 and POLA2) and two primase subunits (PRIM1 and PRIM2). The complex is uniquely responsible for synthesizing short RNA-DNA primers that are subsequently elongated by high-fidelity polymerases delta and epsilon during S-phase. Due to its central role in cell proliferation, Pol α-primase is a major therapeutic target for anticancer agents, particularly nucleoside analogs like cytarabine and gemcitabine, which inhibit DNA synthesis and trigger apoptosis in rapidly dividing cells. Additionally, viral DNA polymerases with analogous functions are critical targets for antiviral therapies used to treat infections such as Hepatitis B and Herpes simplex virus.
Inhibition of DNA synthesis through competitive inhibition of dNTP binding or chain termination following incorporation into the growing DNA strand.
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