DNA Polymerase Delta Function in Replication and Repair
Summary
DNA polymerase delta (Pol δ) is a central enzyme in eukaryotic genome duplication and maintenance, operating as a four-subunit holoenzyme composed of one catalytic subunit (POLD1) and three accessory subunits (POLD2, POLD3, POLD4). During S phase, Pol δ is loaded onto DNA by the sliding clamp proliferating cell nuclear antigen (PCNA) and carries out high-fidelity synthesis of the lagging strand via repeated extension of Okazaki fragments. Its intrinsic 3′→5′ exonuclease activity ensures proofreading and correction of misincorporated nucleotides. Beyond replication, Pol δ fulfils gap-filling roles in several DNA repair pathways, including base excision repair and mismatch repair. Dynamic regulation of its subunit composition—for example, proteolytic removal of POLD4 in response to DNA damage—modulates its activity and substrate specificity, thus safeguarding genome stability under replicative stress.
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DNA Polymerase Delta Function in Replication and Repair publication trend
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Technical terms
Holoenzyme: The complete, catalytically active multi-subunit complex of Pol δ bound to PCNA.
Proliferating cell nuclear antigen (PCNA): A ring-shaped sliding clamp that tethers Pol δ to DNA, enhancing processivity.
Okazaki fragment: Short DNA segment synthesised on the lagging strand, later joined by ligase.
Proofreading exonuclease: The 3′→5′ exonuclease activity of Pol δ that removes mispaired nucleotides to ensure replication fidelity.
Cryo-electron microscopy (cryo-EM): A structural biology technique for visualising macromolecular complexes at near-atomic resolution in a frozen, hydrated state.
References
- POLD4 Promotes Glioma Cell Proliferation and Suppressive Immune Microenvironment: A Pan-Cancer Analysis Integrated with Experimental Validation. International Journal of Molecular Sciences (2023).
- Prospects of POLD1 in Human Cancers: A Review. Cancers (2023).
- Cryo-EM structure of apo-form human DNA polymerase δ elucidates its minimal DNA synthesis activity without PCNA. Journal of Biological Chemistry (2025).
- A Novel DNA Damage Response RAPID DEGRADATION OF THE p12 SUBUNIT OF DNA POLYMERASE δ*. Journal of Biological Chemistry (2007).
- Regulation and Modulation of Human DNA Polymerase δ Activity and Function. Genes (2017).
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