As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24035200, PubMed:24022480). Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine, 8oxoG or abasic sites (PubMed:19074196, PubMed:24191025). a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1) Binds 1 [4Fe-4S] cluster. Regulated by alteration of quaternary structure. Exhibits burst rates of DNA synthesis are about 5 times faster in the presence of POLD4 (Pol-delta4 complex) than in its absence (Pol-delta3 complex), while the affinity of the enzyme for its DNA and dNTP substrates appears unchanged. The Pol-delta3 complex is more likely to proofread DNA synthesis because it cleaves single-stranded DNA twice as fast and transfers mismatched DNA from the polymerase to the exonuclease sites 9 times faster compared to the Pol-delta3 complex. Pol-delta3 also extends mismatched primers 3 times more slowly in the absence of POLD4. The conversion of Pol-delta4 into Pol-delta3 is induced by genotoxic stress or by replication stress leading POLD4 degradation (PubMed:19074196, PubMed:20334433). Stimulated in the presence of PCNA (PubMed:11328591, PubMed:12403614, PubMed:12522211, PubMed:16510448, PubMed:24022480, PubMed:24939902). This stimulation is further increased in the presence of KCTD13/PDIP1, most probably via direct interaction between KCTD13 and POLD2 (By similarity). kcat is 87 sec(-1) for DNA synthesis by Pol-delta4 and 19 sec(-1) for Pol-delta3. kcat for exonuclease activity determined using a 26mer/40mer duplex DNA gives a value of 0.003 sec(-1) for Pol-delta4 and 0.026 sec(-1) for Pol-delta3. When using a 26mer/40mer with a T:G mismatch at the primer terminus, the switching rates from the polymerase to the exonuclease site for Pol-delta4 and Pol-delta3 are increased 20- and 10-fold, respectively, but the rate constant for Pol-delta3 is still 5-fold faster than that for Pol-delta4. 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, PubMed:12522211, PubMed:17317665, PubMed:22801543). Within Pol-delta4, directly interacts with POLD2 and POLD4 (PubMed:11328591, PubMed:12403614, PubMed: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, PubMed: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, PubMed:20334433). Directly interacts with PCNA, as do POLD3 and POLD4; this interaction stimulates Pol-delta4 polymerase activity (PubMed:11328591, PubMed:12403614, PubMed:12522211, PubMed:16510448, PubMed:24022480, PubMed: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). Colocalizes with PCNA and POLD3 at S phase replication sites (PubMed:11595739). After UV irradiation, recruited to DNA damage sites within 2 hours, independently on the cell cycle phase, nor on PCNA ubiquitination. This recruitment requires POLD3, PCNA and RFC1-replication factor C complex (PubMed:20227374, PubMed:22801543). Widely expressed, with high levels of expression in heart and lung. Expression is cell cycle-dependent, with highest levels in G2/M phase and lowest in G1. Up-regulated by serum stimulation. The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes. Disease susceptibility is associated with variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Belongs to the DNA polymerase type-B family.