POLD1

Cancer-related genes, Disease related genes, Enzymes, Metabolic proteins, Plasma proteins, Potential drug targets

Intracellular

Cell type enhanced (Paneth cells, Spermatogonia)

Low immune cell specificity

Low cell line specificity

Component of the tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing both DNA polymerase and 3' to 5' proofreading exonuclease activities (PubMed:11595739, 12522211, 17317665, 22801543). Within Pol-delta4, directly interacts with POLD2 and POLD4 (PubMed:11328591, 12403614, 16510448). Following genotoxic stress by DNA-damaging agents, such as ultraviolet light and methyl methanesulfonate, or by replication stress induced by treatment with hydroxyurea or aphidicolin, Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3) by POLD4 degradation. Pol-delta3 is the major form at S phase replication sites and DNA damage sites (PubMed:22801543, 17317665). POLD1 displays different catalytic properties depending upon the complex it is found in (PubMed:17317665). It exhibits higher proofreading activity and fidelity than Pol-delta4, making it particularly well suited to respond to DNA damage (PubMed:19074196, 20334433). Directly interacts with PCNA, as do POLD3 and POLD4; this interaction stimulates Pol-delta4 polymerase activity (PubMed:11328591, 12403614, 12522211, 16510448, 24022480, 24939902). As POLD2 and POLD4, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA. This stimulation may be due predominantly to an increase of initiation frequency and also to increased processivity (PubMed:15670210). Also observed as a dimeric complex with POLD2 (Pol-delta2 complex). Pol-delta2 is relatively insensitive to the PCNA stimulation (2-5-fold) compared to Pol-delta4 that is stimulated by over 50-fold (PubMed:12403614). The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2 (PubMed:12522211). Interacts with CIAO1 (PubMed:23891004). Interacts with POLDIP2 (PubMed:24191025).

DNA-binding, DNA-directed DNA polymerase, Exonuclease, Hydrolase, Nuclease, Nucleotidyltransferase, Transferase