Recombinant Human DNA polymerase epsilon catalytic subunit A (POLE POLE1)

1. Data suggest that DNA polymerase epsilon catalytic subunit (POLE) mutation does not serve as a relevant biomarker and should not be tested on a regular basis in pancreatic ductal adenocarcinoma (PDAC). PMID: 30194485
2. These findings support a role for E2 beyond E1 recruitment in human papillomavirus 11 DNA replication, and further implicate cellular pol epsilon in viral DNA replication. PMID: 29895728
3. Clinical impact of endometrial cancer stratified by genetic mutational profiles, POLE mutation, and microsatellite instability PMID: 29659608
4. Mutation in DNA Polymerase II gene is associated with MMR deficiency in cancer. PMID: 28512192
5. Meta-analysis found that POLE proofreading domain mutations identify a subset of immunogenic colorectal cancers with excellent prognosis. PMID: 28404093
6. This is the first study to functionally analyze a POLE genetic variant outside the exonuclease domain and widens the spectrum of genetic changes in this DNA polymerase that could lead to colorectal cancer predisposition. PMID: 28423643
7. Mutational analysis of hypermutation-related POLE gene in acute leukemias and lymphomas. PMID: 28034776
8. The basic biochemical mechanisms leading to a unique phenotype in POLE deficiency as well as challenges faced with interpreting the genomic profiling of tumors in this important subset of patients and the potential clinical implications will be discussed here PMID: 28465371
9. Data show that the POLE mutation leading to hypermutation can accelerate cancer development. PMID: 27612425
10. The POLE mutations have in selecting for mutations of the beta2 microglobulin (B2M) gene involved in antigen presentation. PMID: 29320758
11. POLE exonuclease domain mutations are prognostic markers associated with excellent outcomes for endometrial carcinoma patients. PMID: 26763250
12. Case Reports: POLE heterozygous mutations were found in two colorectal adenocarcinomas. PMID: 29072370
13. POLE mutations in tumors of women with grade 3 EEC are associated with a lower risk of recurrence and death, although not statistically significant because of high variability in these estimates. PMID: 26937754
14. We present the case of a patient with a left frontal glioblastoma with primitive neuroectodermal tumor features and hypermutated genotype in the setting of a POLE germline alteration PMID: 27683556
15. Frameshift mutation in POLE gene is associated with mismatch repair-deficiency and Lynch syndrome. PMID: 28218421
16. POLE-mutated undifferentiated and dedifferentiated endometrial carcinomas were more frequently stage I tumors than similar carcinomas lacking exonuclease domain mutations (7/9; 78% vs. 3/12; 25%; P=0.023) and patients had significantly better outcome (disease-specific survival) than those without POLE exonuclease domain mutations (P=0.02) PMID: 28498284
17. In colorectal cancers, mutations in the FBXW7 gene were more common in the younger cohort (27.5% vs 9.7%; P = .0022) as were mutations in the proofreading domain of polymerase epsilon catalytic subunit (POLE) (9.8% vs 1%; P = .0048). PMID: 27244218
18. POLE ultra-mutated endometrial-carcinomas are heavily infiltrated with CD4+/CD8+ TIL, overexpress PD-1 immune-check-point, and have a better prognosis when compared to other molecular subtypes of endometrial-carcinomas patients. POLE-mutated tumor-cell lines are resistant to platinum-chemotherapy in-vitro suggesting that the better prognosis of POLE-patients is not secondary to a higher sensitivity to ch PMID: 27894751
19. Tumors with POLE EDMs had the most favorable prognosis, and those with p53 abn the worst prognosis, and separation of the 2 middle survival curves (p53 wt and MMR-D) was observed PMID: 28061006
20. POLE1 is phosphorylated at serine-1940 after DNA damage and interacts with the iron-sulfur complex chaperones CIAO1 and MMS19. PMID: 27235625
21. POLE-mutated endometrial carcinomas are typically of high grade, with prominent lymphocytic infiltration, but they are not sufficiently distinctive to allow accurate diagnosis based on routine haematoxylin and eosin staining PMID: 26416160
22. Study identified a high penetrant duplication in the regulatory region of GREM1, predisposing to colorectal cancer (CRC) in a family with attenuated/ atypical polyposis. A POLE variant was also identified in a patient with early onset CRC. PMID: 26493165
23. POLE mutations are associated with cutaneous melanoma. PMID: 26251183
24. Identified a genomically, histologically, and clinically distinct subgroup of high-grade gliomas that harbored somatic POLE mutations and carried an improved prognosis. PMID: 25740784
25. Missense point mutations in POLE gene is associated with Ovarian Endometrioid Carcinoma. PMID: 26166557
26. A novel c.1373A>T (p.Tyr458Phe)POLE mutation associated with cancers of colon, pancreas, ovaries and small intestine. PMID: 25860647
27. POLE proofreading-mutant endometrial cancers are characterized by a robust intratumoral T-cell response, which correlates with, and may be caused by an enrichment of antigenic neopeptides PMID: 25878334
28. Results show that that mutated POLE 1 are associated with high neoantigen loads and may be excellent candidates for PD-1-targeted immunotherapies. PMID: 26181000
29. the recognition of ultramutated endometrial carcinomas with POLE exonuclease domain mutation is important given their favorable outcome PMID: 25394778
30. The kinetic parameters of the truncated catalytic subunit and holoenzyme of human DNA polymerase varepsilon are compared. PMID: 25684708
31. POLE ultra-mutated-tumors are significantly more immunogenic when compared to POLE (-) tumors, in particular to the helper arm of the immune system. PMID: 25931171
32. Data indicate that the polymerase (DNA directed), epsilon protein (POLE) mutation c.1270C>G;p.Leu424Val was detected in 1.5% (4/266) of all patients, 4% (3/77) of all familial cases and 7% (2/30) of familial polyposis cases. PMID: 25529843
33. Data indicate that exonuclease domain of DNA polymerase epsilon (POLE-exo*) mutants generate a unique pattern of replication errors. PMID: 25228659
34. Somatic POLE exonuclease domain mutations are common in endometrioid endometrial cancer, are observed with equal frequency in tumors with microsatellite stability and those with microsatellite instability, and are not associated with survival. PMID: 25224212
35. Hearing ability was strongly associated with DNA methylation levels in the promoter regions of several genes, including TCF25, FGFR1, and POLE. PMID: 25184702
36. The 3'-->5' exonuclease activity of hPol further enhances polymerization fidelity by an unprecedented 3.5 x 10(2) to 1.2 x 10(4)-fold. PMID: 25414327
37. POLE mutations have been found in other tumor types, though at lower frequency, suggesting roles in tumorigenesis more broadly in different tissue types. [Review] PMID: 24861832
38. A new amino-acid substitution in POLE was identified resulting in a predisposition to a broad spectrum of tumours in addition to colorectal cancers. PMID: 24788313
39. POLE exonuclease domain mutations occur in a subset of grade 3 endometrioid carcinomas and are associated with good clinical outcome. PMID: 24844595
40. Mutant Pol epsilon causes replication errors in vivo. In colorectal patients, the single allele mutations are microsatellite stable with a large increase in base pair substitutions, consistent with requirement of additional factors for tumor development. PMID: 24051051
41. Heterozygosity for the variant allele caused a strong mutator effect comparable with that of complete mismatch repair deficiency, providing an explanation for why loss of heterozygosity is not required for the development of Polepsilon-mutant human tumors. PMID: 24525744
42. The POLE1 p.S297F mutation was frequent in Chinese ovarian endometrioid carcinoma. PMID: 24472300
43. To catalyze leading-strand synthesis in vivo, Polepsilon likely interacts with its three smaller subunits and additional replication factors in order to assemble a replication complex and significantly enhance its polymerization processivity. PMID: 24020356
44. observed impairment in proliferation and G1- to S-phase progression in patients' T lymphocytes. Polepsilon1 depletion also impaired G1- to S-phase progression in B lymphocytes, chondrocytes, and osteoblasts. PMID: 23230001
45. Pol epsilon is a likely source of ribonucleotides in human genomic DNA. PMID: 23093410
46. Data show that using a 200-nt primed circular DNA substrate, the combined action of DNA polymerase epsilon and the Cdc45/Mcm2-7/GINS (CMG complex) leads to the formation of products >10 kb in length. PMID: 22474384
47. Mutation in the POLE gene that encodes p261 catalytic subunit of pol epsilon is the first found in human cells. PMID: 21157497
48. SNPs associated with prognosis of lung cancer was mapped to POLE. PMID: 17855454
49. An AATT deletion in the 55 kDa small subunit DNA sequence of DNA polymerase epsilon is associated with breast cancer PMID: 19129559

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HGNC: 9177

OMIM: 174762

KEGG: hsa:5426

STRING: 9606.ENSP00000322570

UniGene: Hs.524871