POLD3

The DNA polymerase delta complex is involved in DNA replication and repair, and it consists of the proliferating cell nuclear antigen (PCNA; MIM 176740), the multisubunit replication factor C (see MIM 102579), and the 4 subunit polymerase complex: POLD1 (MIM 174761), POLD2 (MIM 600815), POLD3, and POLD4 (MIM 611525) (Liu and Warbrick, 2006 [PubMed 16934752]).[supplied by OMIM

polymerase (DNA-directed), delta 3, accessory subunit

Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex (PubMed:22801543, PubMed:17317665, PubMed:24449906).
As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA (PubMed:10219083, PubMed:10852724, PubMed:11595739, PubMed:16510448, PubMed:24035200).
Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433).
Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also 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. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites (PubMed:20227374).
Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611).
Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion (PubMed:19074196, PubMed:25628356, PubMed:27185888).
Also involved in TLS, as a component of the tetrametric DNA polymerase zeta complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906).

DNA biosynthetic processManual Assertion Based On ExperimentIDA:UniProtKB
DNA strand elongation involved in DNA replicationManual Assertion Based On ExperimentIBA:GO_Central
DNA synthesis involved in DNA repair1 PublicationNAS:UniProtKB
DNA synthesis involved in UV-damage excision repairManual Assertion Based On ExperimentIBA:GO_Central
DNA-templated DNA replicationManual Assertion Based On ExperimentIDA:ComplexPortal
Error-prone translesion synthesisManual Assertion Based On ExperimentIDA:ComplexPortal
Mismatch repair1 PublicationNAS:UniProtKB
Nucleotide-excision repair, DNA gap fillingManual Assertion Based On ExperimentIMP:UniProtKB

Cytoplasm
Nucleus
Partially colocalizes with PCNA and POLD1 at S phase replication sites (PubMed:11595739).
Recruited to DNA damage sites within 2 hours following UV irradiation (PubMed:20227374, PubMed:22801543).

Ubiquitinated, but not targeted to the proteasome (PubMed:16934752).
Sumoylated (PubMed:16934752, PubMed:25218447).
Sumoylation with SUMO3 may be predominant (PubMed:16934752).
Phosphorylation at Ser-458 is catalyzed in vitro by PKA. It is thought to decrease the affinity for PCNA and Pol-delta4 processivity (PubMed:22148433).
Can also be phosphorylated in vitro by CDK1-cyclin-A complex, as well as CDK2-cyclin-A and CDK2-cyclin-E complexes. PCNA interferes with CDK-cyclin phosphorylation (PubMed:11595739).