DNA polymerase epsilon catalytic subunit A

Function

Catalytic component of the DNA polymerase epsilon complex. Participates in chromosomal DNA replication (By similarity). Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork (By similarity). Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication (By similarity). Involved in DNA synthesis during DNA repair. Along with DNA polymerase POLD1 and DNA polymerase POLK, has a role in excision repair (NER) synthesis following UV irradiation.

Classification

Family (Pfam)

PF03104 DNA_pol_B_exo1, PF08490 DUF1744, PF22634 POL2_thumb, PF22912 zf-DPOE, PF23250 zf_DPOE_2

InterPro

DNA-dir_DNA_pol_B, DNA-dir_DNA_pol_B_exonuc, DNA/RNA_pol_sf, DNA_pol_B_thumb, DNA_pol_e_suA_C, DNA_pol_palm_dom_sf, POL2, POL2_thumb, RNaseH-like_sf, RNaseH_sf, Znf-DPOE

Functional cluster

Oxidoreductases, Catalases & Peroxidases

Experimental structures · PDB · 17

• 5VBN X-ray 2.35A
• 7PFO EM 3.20A
• 7PLO EM 2.80A
• 9B8S EM 5.01A
• 9B8T EM 2.95A
• 9F6D EM 3.60A
• 9F6E EM 3.74A
• 9F6F EM 3.75A
• 9F6I EM 3.30A
• 9F6J EM 3.90A
• 9F6K EM 4.20A
• 9F6L EM 3.90A
• … and 5 more

A predicted model is available from AlphaFold.

Gene Ontology · 21

• GO:0008622 epsilon DNA polymerase complex
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0051539 4 iron, 4 sulfur cluster binding
• GO:0003682 chromatin binding
• GO:0003677 DNA binding
• GO:0003887 DNA-directed DNA polymerase activity
• GO:0000166 nucleotide binding
• GO:0008310 single-stranded DNA 3'-5' DNA exonuclease activity
• GO:0008270 zinc ion binding
• GO:0006287 base-excision repair, gap-filling
• GO:0006260 DNA replication
• GO:0045004 DNA replication proofreading
• GO:0000731 DNA synthesis involved in DNA repair
• GO:0006261 DNA-templated DNA replication
• GO:0048568 embryonic organ development
• GO:0000082 G1/S transition of mitotic cell cycle
• GO:0006272 leading strand elongation
• GO:0000278 mitotic cell cycle
• GO:0006297 nucleotide-excision repair, DNA gap filling

Disease associations

• colorectal cancer, susceptibility to, 12 MONDO:0014038
• facial dysmorphism-immunodeficiency-livedo-short stature syndrome MONDO:0014058
• intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency MONDO:0032684

Drugs targeting this protein · 6

• FLUDARABINE PHOSPHATE inhibitor
• GEMCITABINE HYDROCHLORIDE inhibitor
• CLOFARABINE inhibitor
• TROXACITABINE inhibitor
• ASPACYTARABINE inhibitor
• CYTARABINE inhibitor

Related proteins · sequence + function similarity

• DNA polymerase epsilon catalytic subunit A 0.99
• DNA polymerase epsilon catalytic subunit A 0.97
• DNA polymerase epsilon catalytic subunit 1 0.97
• DNA polymerase epsilon catalytic subunit A 0.96
• DNA polymerase epsilon catalytic subunit A 0.96
• DNA polymerase epsilon catalytic subunit B 0.96
• DNA polymerase epsilon catalytic subunit A 0.95
• DNA polymerase epsilon catalytic subunit A 0.94
• DNA polymerase epsilon catalytic subunit A 0.94
• DNA polymerase epsilon catalytic subunit A 0.94
• DNA polymerase epsilon catalytic subunit A 0.94
• DNA polymerase epsilon catalytic subunit A 0.94

Co-cited proteins · studied together in the literature

• DNA polymerase delta catalytic subunit 3 shared papers
• DNA polymerase epsilon subunit 4 1 shared papers
• DNA polymerase epsilon subunit 2 3 shared papers
• Cell cycle checkpoint protein RAD17 1 shared papers
• DNA topoisomerase 2-binding protein 1 1 shared papers
• DNA polymerase epsilon subunit 3 1 shared papers
• Bone morphogenetic protein receptor type-1A 1 shared papers
• Exonuclease 1 1 shared papers
• Cell cycle checkpoint protein RAD17 1 shared papers
• Serine/threonine-protein kinase B-raf 1 shared papers
• Chromosome transmission fidelity protein 18 homolog 1 shared papers
• DNA polymerase delta subunit 2 1 shared papers

Literature · 18 cited papers

• A conserved mechanism for regulating replisome disassembly in eukaryotes. Nature · 2021
• Structure of a human replisome shows the organisation and interactions of a DNA replication machine. EMBO J. · 2021
• DNA polymerase epsilon deficiency causes IMAGe syndrome with variable immunodeficiency. Am. J. Hum. Genet. · 2018
• The somatic POLE P286R mutation defines a unique subclass of colorectal cancer featuring hypermutation, representing a potential genomic biomarker for immunotherapy. Oncotarget · 2016
• A novel germline POLE mutation causes an early onset cancer prone syndrome mimicking constitutional mismatch repair deficiency. Fam. Cancer · 2017
• A novel POLE mutation associated with cancers of colon, pancreas, ovaries and small intestine. Fam. Cancer · 2015
• New insights into POLE and POLD1 germline mutations in familial colorectal cancer and polyposis. Hum. Mol. Genet. · 2014
• Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat. Genet. · 2013
• Polymerase epsilon1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature (FILS syndrome). J. Exp. Med. · 2012
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Mol. Cell · 2010
• … and 6 more in the literature graph