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DNA polymerase is a fundamental enzyme responsible for synthesizing new DNA strands by adding nucleotides to a template, a process essential for both DNA replication and repair [1][2]. In the context of the DNA replication machinery, it works in coordination with other proteins like helicases, primases, and sliding clamps to ensure genomic integrity during the cell cycle [2]. Because rapid cell division is a hallmark of both cancer and viral replication, DNA polymerases are critical therapeutic targets [3]. Antiviral drugs, such as acyclovir, often act as nucleoside analogs that cause premature chain termination once incorporated into the viral DNA strand by the viral polymerase [4]. Similarly, chemotherapeutic agents like cytarabine inhibit human DNA polymerases to halt the proliferation of malignant cells in leukemias and solid tumors [5]. However, targeting these enzymes can lead to significant side effects, such as myelosuppression, due to the unintended inhibition of DNA synthesis in healthy, rapidly dividing host cells [5].
Inhibition of DNA synthesis through competitive binding with endogenous deoxyribonucleotides at the polymerase active site, leading to DNA chain termination or the formation of defective DNA strands that trigger apoptosis.
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