POLE (gene) explained

DNA polymerase epsilon catalytic subunit is an enzyme that in humans is encoded by the POLE gene.^{[1] [2]} It is the central catalytic subunit of DNA polymerase epsilon.

Clinical significance

POLE, along with POLD1, has in 2013 been associated with multiple adenoma.^[3]

Interactions

POLE has been shown to interact with RAD17.^[4]

References

Further reading

• Popanda O, Thielmann HW . The function of DNA polymerases in DNA repair synthesis of ultraviolet-irradiated human fibroblasts. . Biochim. Biophys. Acta . 1129 . 2 . 155–60 . 1992 . 1730053 . 10.1016/0167-4781(92)90480-N .
• Kesti T, Frantti H, Syväoja JE . Molecular cloning of the cDNA for the catalytic subunit of human DNA polymerase epsilon. . J. Biol. Chem. . 268 . 14 . 10238–45 . 1993 . 10.1016/S0021-9258(18)82195-0 . 8486689 . free .
• Mozzherin DJ, Fisher PA . Human DNA polymerase epsilon: enzymologic mechanism and gap-filling synthesis. . Biochemistry . 35 . 11 . 3572–7 . 1996 . 8639508 . 10.1021/bi952142p .
• Cujec TP, Cho H, Maldonado E, Meyer J, Reinberg D, Peterlin BM . The human immunodeficiency virus transactivator Tat interacts with the RNA polymerase II holoenzyme. . Mol. Cell. Biol. . 17 . 4 . 1817–23 . 1997 . 9121429 . 232028 . 10.1128/mcb.17.4.1817.
• Coll JM, Hickey RJ, Cronkey EA, Jiang HY, Schnaper L, Lee MY, Uitto L, Syvaoja JE, Malkas LH . Mapping specific protein-protein interactions within the core component of the breast cell DNA synthesome. . Oncol. Res. . 9 . 11–12 . 629–39 . 1998 . 9563011 .
• Huang D, Pospiech H, Kesti T, Syväoja JE . Structural organization and splice variants of the POLE1 gene encoding the catalytic subunit of human DNA polymerase epsilon. . Biochem. J. . 339 . 3 . 657–65 . 1999 . 10215605 . 1220202 . 10.1042/0264-6021:3390657 .
• Araújo SJ, Tirode F, Coin F, Pospiech H, Syväoja JE, Stucki M, Hübscher U, Egly JM, Wood RD . Nucleotide excision repair of DNA with recombinant human proteins: definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK. . Genes Dev. . 14 . 3 . 349–59 . 2000 . 10.1101/gad.14.3.349 . 10673506 . 316364 .
• Li Y, Pursell ZF, Linn S . Identification and cloning of two histone fold motif-containing subunits of HeLa DNA polymerase epsilon. . J. Biol. Chem. . 275 . 30 . 23247–52 . 2000 . 10801849 . 10.1074/jbc.M002548200 . free .
• Mäkiniemi M, Hillukkala T, Tuusa J, Reini K, Vaara M, Huang D, Pospiech H, Majuri I, Westerling T, Mäkelä TP, Syväoja JE . BRCT domain-containing protein TopBP1 functions in DNA replication and damage response. . J. Biol. Chem. . 276 . 32 . 30399–406 . 2001 . 11395493 . 10.1074/jbc.M102245200 . free .
• Fuss J, Linn S . Human DNA polymerase epsilon colocalizes with proliferating cell nuclear antigen and DNA replication late, but not early, in S phase. . J. Biol. Chem. . 277 . 10 . 8658–66 . 2002 . 11741962 . 10.1074/jbc.M110615200 . free .
• Ohta S, Shiomi Y, Sugimoto K, Obuse C, Tsurimoto T . A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein. . J. Biol. Chem. . 277 . 43 . 40362–7 . 2002 . 12171929 . 10.1074/jbc.M206194200 . free .
• Post SM, Tomkinson AE, Lee EY . The human checkpoint Rad protein Rad17 is chromatin-associated throughout the cell cycle, localizes to DNA replication sites, and interacts with DNA polymerase epsilon. . Nucleic Acids Res. . 31 . 19 . 5568–75 . 2003 . 14500819 . 206465 . 10.1093/nar/gkg765 .
• Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM . Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region. . Genomics . 83 . 1 . 153–67 . 2004 . 14667819 . 10.1016/S0888-7543(03)00235-0 .
• Clark AG, Glanowski S, Nielsen R, Thomas PD, Kejariwal A, Todd MA, Tanenbaum DM, Civello D, Lu F, Murphy B, Ferriera S, Wang G, Zheng X, White TJ, Sninsky JJ, Adams MD, Cargill M . Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios. . Science . 302 . 5652 . 1960–3 . 2003 . 14671302 . 10.1126/science.1088821 . 2003Sci...302.1960C . 6682593 .
• Rytkönen AK, Vaara M, Nethanel T, Kaufmann G, Sormunen R, Läärä E, Nasheuer HP, Rahmeh A, Lee MY, Syväoja JE, Pospiech H . Distinctive activities of DNA polymerases during human DNA replication. . FEBS J. . 273 . 13 . 2984–3001 . 2006 . 16762037 . 10.1111/j.1742-4658.2006.05310.x . 32819159 .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry. . Mol. Syst. Biol. . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .

Notes and References

1. Szpirer J, Pedeutour F, Kesti T, Riviere M, Syväoja JE, Turc-Carel C, Szpirer C . Localization of the gene for DNA polymerase epsilon (POLE) to human chromosome 12q24.3 and rat chromosome 12 by somatic cell hybrid panels and fluorescence in situ hybridization . Genomics . 20 . 2 . 223–6 . Aug 1994 . 8020968 . 10.1006/geno.1994.1156 .
2. Web site: Entrez Gene: POLE polymerase (DNA directed), epsilon.
3. Palles C, Cazier JB, Howarth KM, Domingo E, Jones AM, Broderick P, Kemp Z, Spain SL, Guarino E, Guarino Almeida E, Salguero I, Sherborne A, Chubb D, Carvajal-Carmona LG, Ma Y, Kaur K, Dobbins S, Barclay E, Gorman M, Martin L, Kovac MB, Humphray S, Lucassen A, Holmes CC, Bentley D, Donnelly P, Taylor J, Petridis C, Roylance R, Sawyer EJ, Kerr DJ, Clark S, Grimes J, Kearsey SE, Thomas HJ, McVean G, Houlston RS, Tomlinson I . Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas . Nat. Genet. . 45 . 2 . 136–44 . 2013 . 23263490 . 3785128 . 10.1038/ng.2503 .
4. Post SM, Tomkinson AE, Lee EY . Eva Y.-H. P. Lee . The human checkpoint Rad protein Rad17 is chromatin-associated throughout the cell cycle, localizes to DNA replication sites, and interacts with DNA polymerase epsilon . Nucleic Acids Res. . 31 . 19 . 5568–75 . Oct 2003 . 14500819 . 206465 . 10.1093/nar/gkg765 . England .