DNA polymerase delta complex (Pol δ)

DNA polymerase delta (Pol δ) is a high-fidelity, multi-subunit enzyme complex that serves as a cornerstone of the eukaryotic DNA replication machinery. Its primary role is the synthesis of the lagging strand, where it extends Okazaki fragments initiated by the DNA polymerase alpha-primase complex (UniProt: P28340). Pol δ is distinguished by its 3' to 5' exonuclease activity, which allows for proofreading and ensures the high accuracy of genome duplication (Nature Reviews Molecular Cell Biology, 2017). In addition to replication, the complex is vital for several DNA repair pathways, including nucleotide excision repair (NER) and mismatch repair (MMR) (PubMed: 28343154). Mutations in the POLD1 gene, which encodes the catalytic subunit, are linked to polymerase proofreading-associated polyposis (PPAP), significantly increasing the risk of colorectal and endometrial cancers (NIH: Genetics Home Reference). Therapeutically, Pol δ is a functional target for various nucleoside analogs and antimetabolites, such as cytarabine and gemcitabine, which inhibit DNA synthesis and induce apoptosis in rapidly dividing cancer cells (PubChem).

Other names

DNA polymerase deltaPOLD1Okazaki fragment initiation machineryDNA-directed DNA polymerase deltaPol delta

Inhibition of DNA synthesis through competitive binding with deoxyribonucleotide triphosphates (dNTPs) or incorporation into the DNA strand leading to chain termination and replication fork stalling (PubMed: 23447401).