DNA polymerase delta 1, catalytic subunit (POLD1)

DNA polymerase delta 1, catalytic subunit (POLD1) is the essential enzymatic subunit of DNA polymerase delta, a multi-protein complex critical for high-fidelity DNA replication and multiple DNA repair pathways. POLD1 possesses both polymerase activity for DNA chain elongation and a 3'-5' exonuclease domain responsible for proofreading newly synthesized DNA, thereby safeguarding genomic stability. Structurally, POLD1 interacts with accessory subunits and PCNA (proliferating cell nuclear antigen) to ensure processivity and tight coordination during lagging strand synthesis and repair. Pathogenic mutations—particularly those affecting the exonuclease domain—cause defective proofreading, excessive mutagenesis, and genomic instability, most notably associated with various cancers and hereditary syndromes such as polymerase proofreading-associated polyposis. In the tumor setting, POLD1 mutation can elevate the tumor mutation burden, thereby increasing the immunogenicity of otherwise resistant microsatellite-stable cancers, and serving as a biomarker for therapeutic response to immune checkpoint inhibition.

Other names

DNA polymerase delta catalytic subunitPOLDCDC23'-5' exodeoxyribonucleaseDNA polymerase subunit delta p125CDC2 homolog (S. cerevisiae)CRCS10IMD120MDPLpolymerase (DNA directed), delta 1, catalytic subunit 125kDapolymerase (DNA) delta 1, catalytic subunitDPOD1

Drugs targeting DNA replication or repair (e.g., chemotherapies, DNA-damaging agents) may exert their effects in POLD1-deficient contexts by exploiting impaired proofreading or repair capacity. Immune checkpoint inhibitors: Tumors with pathogenic POLD1 mutations and hypermutated profiles may respond better to immune checkpoint blockade due to increased neoantigen load