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 (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24022480, PubMed:24035200, PubMed:31449058). Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24022480, PubMed:24035200). 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)
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, PubMed:31449058, PubMed:31629014). 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:17317665, PubMed:22801543). 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). Interacts with RFC1 (PubMed:31629014)
Widely expressed, with high levels of expression in heart and lung
The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes
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.
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.
An autosomal recessive immunologic disorder manifesting in early childhood with recurrent upper and lower respiratory tract infections, lymphopenia, and hypogammaglobulinemia. Affected individuals may also develop persistent viral infections, particularly of the herpes family. Additional variable features include hearing loss, speech delay, short stature, and mildly impaired intellectual development.
No mutation information available.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to APOLD1, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 8
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT03810339 | Solid Tumor, Advanced Cancer | Toripalimab（JS001） as Monotherapy in Participants With POLE or POLD-1 Mutated and Non-MSI-H Advanced Solid Tumors | PHASE2 | RECRUITING |
| NCT05103969 | Tumors, POLE Exonuclease Domain Mutation, POLD1 Gene Mutation | Cohort of Tumors With POLE/D1 Mutation | N/A | RECRUITING |
| NCT04969029 | Immunotherapy, Adjuvant Therapy, Colon Cancer, MSI-H | Immunotherapy Versus Chemotherapy as Adjuvant Therapy for Colon Cancer With MSI-H or POLE/ POLD1 Mutations | PHASE2 | UNKNOWN |
| NCT05420064 | BRCA1 Mutation, POLD1 Gene Mutation, CDKN2A Mutation, BRCA2 Mutation, POLE Gene Mutation, APC Gene Mutation, ATM Gene Mutation, MLH1 Gene Mutation, BARD1 Gene Mutation, MSH2 Gene Mutation, BRIP1 Gene Mutation, MSH6 Gene Mutation, CHEK2 Gene Mutation, PMS2 Gene Mutation, PALB2 Gene Mutation, EPCAM Gene Mutation, RAD51C Gene Mutation, BMPR1A Gene Mutation, RAD51D Gene Mutation, SMAD4, PTEN Gene Mutation, GREM1 | An Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results | NA | RECRUITING |
| NCT06118658 | Gastric, Colorectal Adenocarcinoma | Chemotherapy Sequential Tislelizumab After Radical Resection in Patients With dMMR/MSI-H or POLE/POLD1 Mutations | PHASE2 | NOT_YET_RECRUITING |
| NCT07461246 | Familial Adenomatous Polyposis (FAP), Attenuated Familial Adenomatous Polyposis (AFAP), MUTYH-Associated Polyposis (MAP), Non-APC/MUTYH Associated Polyposis (NAMP), Gardner Syndrome, Turcot Syndrome, Colorectal Cancer, Desmoid Tumor, Desmoid-Type Fibromatosis, Duodenal Adenoma, Upper Gastrointestinal Polyposis, Hereditary Colorectal Cancer Syndrome, Hereditary Polyposis Syndrome | Familial Adenomatous Poliposys Italian Network (Rete Italiana Poliposi Adenomatosa Familiare) | N/A | ACTIVE_NOT_RECRUITING |
| NCT03428802 | BRCA1 Gene Mutation, BRCA2 Gene Mutation, Locally Advanced Solid Neoplasm, Metastatic Malignant Solid Neoplasm, POLD1 Gene Mutation, POLE Gene Mutation, Recurrent Malignant Solid Neoplasm, Recurrent Ovarian Carcinoma, Stage III Breast Cancer AJCC v7, Stage III Ovarian Cancer AJCC v8, Stage IIIA Breast Cancer AJCC v7, Stage IIIA Ovarian Cancer AJCC v8, Stage IIIB Breast Cancer AJCC v7, Stage IIIB Ovarian Cancer AJCC v8, Stage IIIC Breast Cancer AJCC v7, Stage IIIC Ovarian Cancer AJCC v8, Stage IV Breast Cancer AJCC v6 and v7, Stage IV Ovarian Cancer AJCC v8, Stage IVA Ovarian Cancer AJCC v8, Stage IVB Ovarian Cancer AJCC v8 | Pembrolizumab in Treating Participants With Metastatic, Recurrent or Locally Advanced Cancer and Genomic Instability | PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT03491345 | PD-L1 Positive Mutation Tumor, EBV Positive Mutation Tumor, MSI-H Mutation Tumor, POLE/POLD1 Mutation Tumor | K-Basket, Avelumab, Biomarker-driven, Advanced Solid Tumor | PHASE2 | UNKNOWN |