DNA polymerase alpha (α); DNA polymerase beta (β) (Pol α; Pol β)

DNA polymerase alpha and DNA polymerase beta are central mammalian enzymes required for DNA replication (alpha) and nuclear DNA repair (beta), respectively[2][4][6][10]. Cytarabine, an antimetabolite and nucleoside analog, is a prodrug metabolized to its active triphosphate form (ara-CTP) inside cells, where it inhibits DNA polymerase alpha—hindering DNA replication—and DNA polymerase beta—blocking DNA repair. Additionally, the triphosphate form is incorporated into DNA, resulting in chain termination and apoptosis, particularly in cells actively synthesizing DNA (S-phase)[3][5][1][9]. These processes form the basis for cytarabine's effectiveness (and toxicity) in treating leukemias and other rapidly proliferating malignancies. Notably, resistance can arise via upregulation of translesion synthesis polymerases (e.g., polymerase eta), which are able to bypass the block created by cytarabine incorporation[7][9].

Other names

DNA pol alphaDNA pol βDNA-dependent DNA polymerasesDeoxynucleotidyl transferases

Cytarabine acts as a nucleoside analog that is converted (in cells) to cytarabine-5'-triphosphate (ara-CTP), which inhibits DNA polymerase α (impairing DNA replication) and DNA polymerase β (blocking DNA repair), and gets incorporated into DNA, causing chain termination and cell death