POLD1

POLD1 is the 125-kDa catalytic subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair.

Full Name

DNA Polymerase Delta 1, Catalytic Subunit

Function

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).

Biological Process

Base-excision repair, gap-fillingManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to UVManual Assertion Based On ExperimentIDA:UniProtKB
DNA biosynthetic processManual Assertion Based On ExperimentIDA:UniProtKB
DNA repairManual Assertion Based On ExperimentTAS:ProtInc
DNA replicationManual Assertion Based On ExperimentIMP:UniProtKB
DNA replication proofreadingManual Assertion Based On ExperimentIBA:GO_Central
DNA synthesis involved in DNA repairManual Assertion Based On ExperimentIDA:UniProtKB
DNA-templated DNA replicationManual Assertion Based On ExperimentIDA:ComplexPortal
Error-free translesion synthesisManual Assertion Based On ExperimentIDA:UniProtKB
Fatty acid homeostasisManual Assertion Based On ExperimentIMP:UniProtKB
Nucleotide-excision repair, DNA gap fillingManual Assertion Based On ExperimentIMP:UniProtKB
Response to UVManual Assertion Based On ExperimentTAS:ProtInc

Cellular Location

Nucleus
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).

Involvement in disease

Colorectal cancer 10 (CRCS10):
A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL):
An autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, metabolic abnormalities including insulin resistance and diabetes mellitus, sclerodermatous skin, and a facial appearance characterized by mandibular hypoplasia. Sensorineural deafness occurs late in the first or second decades of life.