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DNA polymerase delta subunit 4 (POLD4, also known as p12) is the smallest accessory subunit of the tetrameric DNA polymerase delta complex, which is a major eukaryotic DNA polymerase required for high-fidelity DNA replication and repair. POLD4 enhances the rate of DNA synthesis and modulates the proofreading activity of the complex by regulating the main catalytic subunit (POLD1). Under replication stress or DNA damage, POLD4 can be degraded, altering the polymerase composition and activity to favor repair and cell survival. POLD4 is implicated in several DNA repair pathways (e.g., base excision repair, Okazaki fragment processing, translesion synthesis), and plays a structural and functional role in maintaining genome stability in dividing cells.
Indirectly, drugs targeting DNA replication may impair DNA polymerase delta activity, often by incorporation of nucleotide analogs or causing DNA damage. Any hypothetical direct POLD4-targeted drug would likely affect DNA replication fidelity, repair, or processivity.
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