TISIDB

Summary
Symbol	POLE
Name	polymerase (DNA directed), epsilon, catalytic subunit
Aliases	POLE1; DNA polymerase epsilon catalytic subunit A; polymerase (DNA directed), epsilon; CRCS12; FILS1; DNA po ......
Chromosomal Location	12q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus.
Domain	PF00136 DNA polymerase family B PF03104 DNA polymerase family B PF08490 Domain of unknown function (DUF1744)
Function	Participates in DNA repair and in chromosomal DNA replication.

> Gene Ontology [ TOP ]
Biological Process	GO:0000082 G1/S transition of mitotic cell cycle GO:0000722 telomere maintenance via recombination GO:0000723 telomere maintenance GO:0000731 DNA synthesis involved in DNA repair GO:0006260 DNA replication GO:0006261 DNA-dependent DNA replication GO:0006270 DNA replication initiation GO:0006284 base-excision repair GO:0006287 base-excision repair, gap-filling GO:0006289 nucleotide-excision repair GO:0006297 nucleotide-excision repair, DNA gap filling GO:0006310 DNA recombination GO:0006312 mitotic recombination GO:0032200 telomere organization GO:0044770 cell cycle phase transition GO:0044772 mitotic cell cycle phase transition GO:0044843 cell cycle G1/S phase transition GO:0048568 embryonic organ development GO:0060249 anatomical structure homeostasis GO:0071897 DNA biosynthetic process GO:0090305 nucleic acid phosphodiester bond hydrolysis
Molecular Function	GO:0003682 chromatin binding GO:0003887 DNA-directed DNA polymerase activity GO:0004518 nuclease activity GO:0004527 exonuclease activity GO:0008408 3'-5' exonuclease activity GO:0016779 nucleotidyltransferase activity GO:0034061 DNA polymerase activity GO:0051536 iron-sulfur cluster binding GO:0051539 4 iron, 4 sulfur cluster binding GO:0051540 metal cluster binding
Cellular Component	GO:0000109 nucleotide-excision repair complex GO:0005657 replication fork GO:0008622 epsilon DNA polymerase complex GO:0030894 replisome GO:0032993 protein-DNA complex GO:0042575 DNA polymerase complex GO:0043596 nuclear replication fork GO:0043601 nuclear replisome GO:0044454 nuclear chromosome part GO:0061695 transferase complex, transferring phosphorus-containing groups GO:1990391 DNA repair complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa03030 DNA replication hsa03410 Base excision repair hsa03420 Nucleotide excision repair hsa00230 Purine metabolism hsa00240 Pyrimidine metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-68962: Activation of the pre-replicative complex R-HSA-73884: Base Excision Repair R-HSA-1640170: Cell Cycle R-HSA-69278: Cell Cycle, Mitotic R-HSA-73886: Chromosome Maintenance R-HSA-73893: DNA Damage Bypass R-HSA-5693532: DNA Double-Strand Break Repair R-HSA-73894: DNA Repair R-HSA-69306: DNA Replication R-HSA-69002: DNA Replication Pre-Initiation R-HSA-68952: DNA replication initiation R-HSA-5696400: Dual Incision in GG-NER R-HSA-6782135: Dual incision in TC-NER R-HSA-180786: Extension of Telomeres R-HSA-69206: G1/S Transition R-HSA-5696397: Gap-filling DNA repair synthesis and ligation in GG-NER R-HSA-6782210: Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-5696399: Global Genome Nucleotide Excision Repair (GG-NER) R-HSA-5693567: HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5685942: HDR through Homologous Recombination (HRR) R-HSA-5693538: Homology Directed Repair R-HSA-68874: M/G1 Transition R-HSA-453279: Mitotic G1-G1/S phases R-HSA-5696398: Nucleotide Excision Repair R-HSA-5651801: PCNA-Dependent Long Patch Base Excision Repair R-HSA-110314: Recognition of DNA damage by PCNA-containing replication complex R-HSA-110373: Resolution of AP sites via the multiple-nucleotide patch replacement pathway R-HSA-73933: Resolution of Abasic Sites (AP sites) R-HSA-69242: S Phase R-HSA-69239: Synthesis of DNA R-HSA-174417: Telomere C-strand (Lagging Strand) Synthesis R-HSA-174430: Telomere C-strand synthesis initiation R-HSA-157579: Telomere Maintenance R-HSA-5656169: Termination of translesion DNA synthesis R-HSA-6781827: Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-110313: Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template

> KEGG and Reactome Pathway

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KEGG

hsa03030 DNA replication
hsa03410 Base excision repair
hsa03420 Nucleotide excision repair
hsa00230 Purine metabolism
hsa00240 Pyrimidine metabolism
hsa01100 Metabolic pathways

Reactome

R-HSA-68962: Activation of the pre-replicative complex
R-HSA-73884: Base Excision Repair
R-HSA-1640170: Cell Cycle
R-HSA-69278: Cell Cycle, Mitotic
R-HSA-73886: Chromosome Maintenance
R-HSA-73893: DNA Damage Bypass
R-HSA-5693532: DNA Double-Strand Break Repair
R-HSA-73894: DNA Repair
R-HSA-69306: DNA Replication
R-HSA-69002: DNA Replication Pre-Initiation
R-HSA-68952: DNA replication initiation
R-HSA-5696400: Dual Incision in GG-NER
R-HSA-6782135: Dual incision in TC-NER
R-HSA-180786: Extension of Telomeres
R-HSA-69206: G1/S Transition
R-HSA-5696397: Gap-filling DNA repair synthesis and ligation in GG-NER
R-HSA-6782210: Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-5696399: Global Genome Nucleotide Excision Repair (GG-NER)
R-HSA-5693567: HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
R-HSA-5685942: HDR through Homologous Recombination (HRR)
R-HSA-5693538: Homology Directed Repair
R-HSA-68874: M/G1 Transition
R-HSA-453279: Mitotic G1-G1/S phases
R-HSA-5696398: Nucleotide Excision Repair
R-HSA-5651801: PCNA-Dependent Long Patch Base Excision Repair
R-HSA-110314: Recognition of DNA damage by PCNA-containing replication complex
R-HSA-110373: Resolution of AP sites via the multiple-nucleotide patch replacement pathway
R-HSA-73933: Resolution of Abasic Sites (AP sites)
R-HSA-69242: S Phase
R-HSA-69239: Synthesis of DNA
R-HSA-174417: Telomere C-strand (Lagging Strand) Synthesis
R-HSA-174430: Telomere C-strand synthesis initiation
R-HSA-157579: Telomere Maintenance
R-HSA-5656169: Termination of translesion DNA synthesis
R-HSA-6781827: Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-110313: Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template

Summary
Symbol	POLE
Name	polymerase (DNA directed), epsilon, catalytic subunit
Aliases	POLE1; DNA polymerase epsilon catalytic subunit A; polymerase (DNA directed), epsilon; CRCS12; FILS1; DNA po ......
Chromosomal Location	12q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between POLE and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between POLE and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29650000	lung adenocarcinoma	Inhibit immunity	POLE-mutant LUAD patients with high expression of PD-L1 (Mut-High, n = 6) exhibited improved OS (P = 0.024) when compared to POLE-mutant patients with low PD-L1 expression (Mut-Low, n = 24) and other patients without POLE mutation (n = 476). This benefit was not due to the high content of the tumor infiltrating lymphocytes. Instead, the antitumor immune response was activated in Mut-High patients so that these patients were likely responding more effectively to immuno-oncology (IO) treatments; whereas genes involved with metabolic pathways were enriched in Mut-Low group, which may cause the decreased OS of these patients.
29604063	colorectal carcinoma； endometrial cancer	Inhibit immunity (T cell function); immunotherapy target	Using genome and exome sequencing, we found that multiple driver mutations in POLE-mutant cancers show the characteristic POLE mutational signature, including those in genes conventionally regarded as initiators of tumourigenesis.
29572003	Non-Small Cell Lung Carcinoma	Inhibit immunity	POLE mutation may thus represent a candidate biomarker for response to immunotherapy in patients with NSCLC.

Summary
Symbol	POLE
Name	polymerase (DNA directed), epsilon, catalytic subunit
Aliases	POLE1; DNA polymerase epsilon catalytic subunit A; polymerase (DNA directed), epsilon; CRCS12; FILS1; DNA po ......
Chromosomal Location	12q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of POLE in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	POLE
Name	polymerase (DNA directed), epsilon, catalytic subunit
Aliases	POLE1; DNA polymerase epsilon catalytic subunit A; polymerase (DNA directed), epsilon; CRCS12; FILS1; DNA po ......
Chromosomal Location	12q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of POLE in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.341	0.234
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.638	0.606
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.124	0.895
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.325	0.285
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.254	0.917
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.42	0.896
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.185	0.565
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.126	0.93
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.275	0.861
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.73	0.538
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.615	0.721
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.357	1.13e-05

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of POLE in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	2.7	4.7	0.294
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	3.4	4	0.587
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	12.5	-1.4	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	14.3	10.7	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	3.7	1.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	7.7	1.4	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	POLE
Name	polymerase (DNA directed), epsilon, catalytic subunit
Aliases	POLE1; DNA polymerase epsilon catalytic subunit A; polymerase (DNA directed), epsilon; CRCS12; FILS1; DNA po ......
Chromosomal Location	12q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of POLE. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	POLE
Name	polymerase (DNA directed), epsilon, catalytic subunit
Aliases	POLE1; DNA polymerase epsilon catalytic subunit A; polymerase (DNA directed), epsilon; CRCS12; FILS1; DNA po ......
Chromosomal Location	12q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of POLE. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by POLE. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	POLE
Name	polymerase (DNA directed), epsilon, catalytic subunit
Aliases	POLE1; DNA polymerase epsilon catalytic subunit A; polymerase (DNA directed), epsilon; CRCS12; FILS1; DNA po ......
Chromosomal Location	12q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of POLE. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	POLE
Name	polymerase (DNA directed), epsilon, catalytic subunit
Aliases	POLE1; DNA polymerase epsilon catalytic subunit A; polymerase (DNA directed), epsilon; CRCS12; FILS1; DNA po ......
Chromosomal Location	12q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of POLE expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	POLE
Name	polymerase (DNA directed), epsilon, catalytic subunit
Aliases	POLE1; DNA polymerase epsilon catalytic subunit A; polymerase (DNA directed), epsilon; CRCS12; FILS1; DNA po ......
Chromosomal Location	12q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between POLE and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	POLE
Name	polymerase (DNA directed), epsilon, catalytic subunit
Aliases	POLE1; DNA polymerase epsilon catalytic subunit A; polymerase (DNA directed), epsilon; CRCS12; FILS1; DNA po ......
Chromosomal Location	12q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting POLE collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting POLE.

ID	Name	Drug Type	Targets	#Targets
DB00242	Cladribine	Small Molecule	PNP, POLA1, POLE, POLE2, POLE3, POLE4, RRM1, RRM2, RRM2B	9

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