Thymine-DNA glycosylase
G/T mismatch-specific thymine DNA glycosylase is an enzyme that in humans is encoded by the TDG gene.[1][2][3]
The protein encoded by this gene belongs to the TDG/mug DNA glycosylase family. Thymine-DNA glycosylase (TDG) removes thymine moieties from G/T mismatches by hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of DNA and the mispaired thymine. With lower activity, this enzyme also removes thymine from C/T and T/T mispairings. TDG can also remove uracil and 5-bromouracil from mispairings with guanine. This enzyme plays a central role in cellular defense against genetic mutation caused by the spontaneous deamination of 5-methylcytosine and cytosine. This gene may have a pseudogene in the p arm of chromosome 12.[3]
Interactions
Thymine-DNA glycosylase has been shown to interact with Estrogen receptor alpha,[4] SUMO3,[5] CREB-binding protein,[6] Promyelocytic leukemia protein[7] and Small ubiquitin-related modifier 1.[8][5]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective Wikipedia articles. [9]
Fluorouracil (5-FU) Activity
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References
- ^ Neddermann P, Gallinari P, Lettieri T, Schmid D, Truong O, Hsuan JJ, Wiebauer K, Jiricny J (Aug 1996). "Cloning and expression of human G/T mismatch-specific thymine-DNA glycosylase". J Biol Chem 271 (22): 12767–74. doi:10.1074/jbc.271.22.12767. PMID 8662714.
- ^ Sard L, Tornielli S, Gallinari P, Minoletti F, Jiricny J, Lettieri T, Pierotti MA, Sozzi G, Radice P (Dec 1997). "Chromosomal localizations and molecular analysis of TDG gene-related sequences". Genomics 44 (2): 222–6. doi:10.1006/geno.1997.4843. PMID 9299239.
- ^ a b "Entrez Gene: TDG thymine-DNA glycosylase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6996.
- ^ Chen, Dongsheng; Lucey Marie J, Phoenix Fladia, Lopez-Garcia Jorge, Hart Stephen M, Losson Régine, Buluwela Lakjaya, Coombes R Charles, Chambon Pierre, Schär Primo, Ali Simak (Oct. 2003). "T:G mismatch-specific thymine-DNA glycosylase potentiates transcription of estrogen-regulated genes through direct interaction with estrogen receptor alpha". J. Biol. Chem. (United States) 278 (40): 38586–92. doi:10.1074/jbc.M304286200. ISSN 0021-9258. PMID 12874288.
- ^ a b Hardeland, Ulrike; Steinacher Roland, Jiricny Josef, Schär Primo (Mar. 2002). "Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover". EMBO J. (England) 21 (6): 1456–64. doi:10.1093/emboj/21.6.1456. ISSN 0261-4189. PMC 125358. PMID 11889051. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125358.
- ^ Tini, Marc; Benecke Arndt, Um Soo-Joong, Torchia Joseph, Evans Ronald M, Chambon Pierre (Feb. 2002). "Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription". Mol. Cell (United States) 9 (2): 265–77. doi:10.1016/S1097-2765(02)00453-7. ISSN 1097-2765. PMID 11864601.
- ^ Takahashi, Hidehisa; Hatakeyama Shigetsugu, Saitoh Hisato, Nakayama Keiichi I (Feb. 2005). "Noncovalent SUMO-1 binding activity of thymine DNA glycosylase (TDG) is required for its SUMO-1 modification and colocalization with the promyelocytic leukemia protein". J. Biol. Chem. (United States) 280 (7): 5611–21. doi:10.1074/jbc.M408130200. ISSN 0021-9258. PMID 15569683.
- ^ Minty, A; Dumont X, Kaghad M, Caput D (Nov. 2000). "Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif". J. Biol. Chem. (UNITED STATES) 275 (46): 36316–23. doi:10.1074/jbc.M004293200. ISSN 0021-9258. PMID 10961991.
- ^ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601". http://www.wikipathways.org/index.php/Pathway:WP1601.
Further reading
- Lindahl T (1982). "DNA repair enzymes". Annu. Rev. Biochem. 51: 61–87. doi:10.1146/annurev.bi.51.070182.000425. PMID 6287922.
- Hardeland U, Bentele M, Lettieri T, et al. (2001). "Thymine DNA glycosylase". Prog. Nucleic Acid Res. Mol. Biol.. Progress in Nucleic Acid Research and Molecular Biology 68: 235–53. doi:10.1016/S0079-6603(01)68103-0. ISBN 9780125400688. PMID 11554300.
- Chevray PM, Nathans D (1992). "Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun". Proc. Natl. Acad. Sci. U.S.A. 89 (13): 5789–93. doi:10.1073/pnas.89.13.5789. PMC 402103. PMID 1631061. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=402103.
- Neddermann P, Jiricny J (1994). "Efficient removal of uracil from G.U mispairs by the mismatch-specific thymine DNA glycosylase from HeLa cells". Proc. Natl. Acad. Sci. U.S.A. 91 (5): 1642–6. doi:10.1073/pnas.91.5.1642. PMC 43219. PMID 8127859. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43219.
- Neddermann P, Jiricny J (1993). "The purification of a mismatch-specific thymine-DNA glycosylase from HeLa cells". J. Biol. Chem. 268 (28): 21218–24. PMID 8407958.
- Barrett TE, Savva R, Panayotou G, et al. (1998). "Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatch recognition by complementary-strand interactions". Cell 92 (1): 117–29. doi:10.1016/S0092-8674(00)80904-6. PMID 9489705.
- Missero C, Pirro MT, Simeone S, et al. (2001). "The DNA glycosylase T:G mismatch-specific thymine DNA glycosylase represses thyroid transcription factor-1-activated transcription". J. Biol. Chem. 276 (36): 33569–75. doi:10.1074/jbc.M104963200. PMID 11438542.
- Tini M, Benecke A, Um SJ, et al. (2002). "Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription". Mol. Cell 9 (2): 265–77. doi:10.1016/S1097-2765(02)00453-7. PMID 11864601.
- Hardeland U, Steinacher R, Jiricny J, Schär P (2002). "Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover". EMBO J. 21 (6): 1456–64. doi:10.1093/emboj/21.6.1456. PMC 125358. PMID 11889051. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125358.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Abu M, Waters TR (2003). "The main role of human thymine-DNA glycosylase is removal of thymine produced by deamination of 5-methylcytosine and not removal of ethenocytosine". J. Biol. Chem. 278 (10): 8739–44. doi:10.1074/jbc.M211084200. PMID 12493755.
- Shimizu Y, Iwai S, Hanaoka F, Sugasawa K (2003). "Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase". EMBO J. 22 (1): 164–73. doi:10.1093/emboj/cdg016. PMC 140069. PMID 12505994. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=140069.
- Chen D, Lucey MJ, Phoenix F, et al. (2003). "T:G mismatch-specific thymine-DNA glycosylase potentiates transcription of estrogen-regulated genes through direct interaction with estrogen receptor alpha". J. Biol. Chem. 278 (40): 38586–92. doi:10.1074/jbc.M304286200. PMID 12874288.
- Lehner B, Semple JI, Brown SE, et al. (2004). "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. doi:10.1016/S0888-7543(03)00235-0. PMID 14667819.
- Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197.
- Krześniak M, Butkiewicz D, Samojedny A, et al. (2005). "Polymorphisms in TDG and MGMT genes - epidemiological and functional study in lung cancer patients from Poland". Ann. Hum. Genet. 68 (Pt 4): 300–12. doi:10.1046/j.1529-8817.2004.00079.x. PMID 15225156.
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PDB gallery
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1wyw: Crystal Structure of SUMO1-conjugated thymine DNA glycosylase
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2d07: Crystal Structure of SUMO-3-modified Thymine-DNA Glycosylase
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