DNA-directed DNA polymerase (host) (DNA pol)

Cellular DNA polymerases, including the alpha, delta, and epsilon isoforms, are fundamental host enzymes that catalyze the synthesis of DNA during replication and repair processes [1, 7]. In the context of antiviral therapy with ganciclovir, these enzymes serve as significant off-targets for the drug's active metabolite, ganciclovir triphosphate (GCV-TP) [1, 2]. GCV-TP competitively inhibits the incorporation of deoxyguanosine triphosphate (dGTP) into the growing DNA strand, which can lead to slowed elongation or premature chain termination in host cells [1, 4]. While ganciclovir is designed to selectively target viral DNA polymerase (such as CMV UL54), its residual affinity for cellular DNA polymerase alpha is the primary driver of hematologic toxicities, most notably myelosuppression [1, 5]. This inhibition results in clinical side effects such as neutropenia, anemia, and thrombocytopenia, necessitating careful monitoring of blood counts during treatment [1, 6]. Consequently, cellular DNA polymerase is a critical factor in determining the therapeutic index and safety profile of nucleoside analog antivirals [2, 4].

Other names

Cellular DNA polymeraseHost DNA polymeraseDNA polymerase alphaDNA polymerase deltaDNA polymerase epsilon

Competitive inhibition of deoxyguanosine triphosphate (dGTP) incorporation into DNA; potential for chain termination or slowing of DNA elongation.