DNA polymerase delta subunit 3 (POLD3)

DNA polymerase delta subunit 3 (POLD3) is an accessory, non-catalytic component of the DNA polymerase delta complex, a key enzyme group required for high-fidelity replication and repair of nuclear DNA in eukaryotic cells[1][2][3][4][5]. POLD3 modulates the activity and structural integrity of the DNA polymerase delta holoenzyme, facilitating lagging strand DNA synthesis and various repair pathways, including homologous recombination, nucleotide excision repair, and break-induced replication[2][4]. By directly interacting with proliferating cell nuclear antigen (PCNA), POLD3 enhances enzyme processivity and is crucial for the recruitment and proper functioning of the polymerase at DNA replication forks and damage sites[1][2][4]. Deficiency or dysfunction of POLD3 leads to genome instability, impaired S-phase progression, accumulation of DNA breaks, and has been linked to certain cancers and immunodeficiencies[1][2]. No drugs are known to selectively inhibit POLD3, but it may be indirectly affected by agents targeting DNA replication more broadly[3][4].

Other names

DNA polymerase delta 3, accessory subunitPOLD3KIAA0039p66p68PPP1R128DNA polymerase delta subunit CDNA polymerase delta subunit p66DNA polymerase delta subunit p68Pol delta C subunit (p66)protein phosphatase 1 regulatory subunit 128IMD122

Not specifically targeted, but inhibition of the DNA polymerase delta complex may impair DNA synthesis and repair, leading to cytotoxicity in rapidly dividing cells (anticancer mechanism by broader polymerase inhibitors)