thymine-DNA glycosylase

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. TDG knockout mouse models showed no increase in mispairing frequency suggesting that other enzymes, like the functional homologue MBD4, may provide functional redundancy. This gene may have a pseudogene in the p arm of chromosome 12.

Additionally, in 2011, the human thymine DNA glycosylase (hTDG) was reported to efficiently excise 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), the key oxidation products of 5-methylcytosine in genomic DNA.{{cite journal |vauthors=He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L, Sun Y, Li X, Dai Q, Song CX, Zhang K, He C, Xu GL | title = Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. | journal = Science | volume = 333 | issue = 6047 | pages = 1303–7 |date=September 2011 | pmid = 21817016 | pmc = 3462231| doi = 10.1126/science.1210944 | bibcode = 2011Sci...333.1303H }} Later on, the crystal structure of the hTDG catalytic domain in complex with duplex DNA containing 5caC was published, which supports the role of TDG in mammalian 5-methylcytosine demethylation.{{cite journal |vauthors=Zhang L, Lu X, Lu J, Liang H, Dai Q, Xu GL, Luo C, Jiang H, He C | title = Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA. | journal = Nature Chemical Biology | volume = 8 | issue = 4 | pages = 328–30 |date=February 2012 | pmid = 22327402 | pmc = 3307914| doi = 10.1038/nchembio.914 }}

Thymine-DNA glycosylase has been shown to interact with:

• CREB-binding protein,{{cite journal |vauthors=Tini M, Benecke A, Um SJ, Torchia J, Evans RM, Chambon P | title = Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription | journal = Mol. Cell | volume = 9 | issue = 2 | pages = 265–77 |date=February 2002 | pmid = 11864601 | doi = 10.1016/S1097-2765(02)00453-7 | doi-access = free }}
• Estrogen receptor alpha,{{cite journal |vauthors=Chen D, Lucey MJ, Phoenix F, Lopez-Garcia J, Hart SM, Losson R, Buluwela L, Coombes RC, Chambon P, Schär P, Ali S | title = T:G mismatch-specific thymine-DNA glycosylase potentiates transcription of estrogen-regulated genes through direct interaction with estrogen receptor alpha | journal = J. Biol. Chem. | volume = 278 | issue = 40 | pages = 38586–92 |date=October 2003 | pmid = 12874288 | doi = 10.1074/jbc.M304286200 | doi-access = free }}
• Promyelocytic leukemia protein,{{cite journal |vauthors=Takahashi H, Hatakeyama S, Saitoh H, Nakayama KI | title = Noncovalent SUMO-1 binding activity of thymine DNA glycosylase (TDG) is required for its SUMO-1 modification and colocalization with the promyelocytic leukemia protein | journal = J. Biol. Chem. | volume = 280 | issue = 7 | pages = 5611–21 |date=February 2005 | pmid = 15569683 | doi = 10.1074/jbc.M408130200 | doi-access = free }}
• SUMO3,{{cite journal |vauthors=Hardeland U, Steinacher R, Jiricny J, Schär P | title = Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover | journal = EMBO J. | volume = 21 | issue = 6 | pages = 1456–64 |date=March 2002 | pmid = 11889051 | pmc = 125358 | doi = 10.1093/emboj/21.6.1456 }} and
• Small ubiquitin-related modifier 1.{{cite journal |vauthors=Minty A, Dumont X, Kaghad M, Caput D | title = Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif | journal = J. Biol. Chem. | volume = 275 | issue = 46 | pages = 36316–23 |date=November 2000 | pmid = 10961991 | doi = 10.1074/jbc.M004293200 | doi-access = free }}

{{FluoropyrimidineActivity WP1601|highlight=Thymine-DNA_glycosylase}}

• DNA-deoxyinosine glycosylase
• SMUG1
• Uracil-DNA glycosylase
• MBD4

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• {{cite journal|author=Lindahl T|title=DNA repair enzymes|journal=Annu. Rev. Biochem.|volume=51|pages=61–87|year=1982|pmid=6287922|doi=10.1146/annurev.bi.51.070182.000425|doi-access=free}}
• {{cite book|vauthors=Hardeland U, Bentele M, Lettieri T, etal|title=Base Excision Repair|chapter=Thymine DNA glycosylase|journal=Prog. Nucleic Acid Res. Mol. Biol.|volume=68|pages=235–53|year=2001|pmid=11554300|doi=10.1016/S0079-6603(01)68103-0|series=Progress in Nucleic Acid Research and Molecular Biology|isbn=978-0-12-540068-8}}
• {{cite journal|vauthors=Chevray PM, Nathans D|title=Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun|journal=Proc. Natl. Acad. Sci. U.S.A.|volume=89|issue=13|pages=5789–93|year=1992|pmid=1631061|doi=10.1073/pnas.89.13.5789|pmc=402103|bibcode=1992PNAS...89.5789C|doi-access=free}}
• {{cite journal|vauthors=Neddermann P, Jiricny J|title=Efficient removal of uracil from G.U mispairs by the mismatch-specific thymine DNA glycosylase from HeLa cells|journal=Proc. Natl. Acad. Sci. U.S.A.|volume=91|issue=5|pages=1642–6|year=1994|pmid=8127859|doi=10.1073/pnas.91.5.1642|pmc=43219|doi-access=free}}
• {{cite journal|vauthors=Neddermann P, Jiricny J|title=The purification of a mismatch-specific thymine-DNA glycosylase from HeLa cells|journal=J. Biol. Chem.|volume=268|issue=28|pages=21218–24|year=1993|doi=10.1016/S0021-9258(19)36913-3|pmid=8407958|doi-access=free}}
• {{cite journal|vauthors=Barrett TE, Savva R, Panayotou G, etal|title=Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatch recognition by complementary-strand interactions|journal=Cell|volume=92|issue=1|pages=117–29|year=1998|pmid=9489705|doi=10.1016/S0092-8674(00)80904-6|s2cid=9136303|doi-access=free}}
• {{cite journal|vauthors=Missero C, Pirro MT, Simeone S, etal|title=The DNA glycosylase T:G mismatch-specific thymine DNA glycosylase represses thyroid transcription factor-1-activated transcription|journal=J. Biol. Chem.|volume=276|issue=36|pages=33569–75|year=2001|pmid=11438542|doi=10.1074/jbc.M104963200|doi-access=free}}
• {{cite journal|vauthors=Tini M, Benecke A, Um SJ, etal|title=Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription|journal=Mol. Cell|volume=9|issue=2|pages=265–77|year=2002|pmid=11864601|doi=10.1016/S1097-2765(02)00453-7|doi-access=free}}
• {{cite journal|vauthors=Hardeland U, Steinacher R, Jiricny J, Schär P|title=Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover|journal=EMBO J.|volume=21|issue=6|pages=1456–64|year=2002|pmid=11889051|doi=10.1093/emboj/21.6.1456|pmc=125358}}
• {{cite journal|vauthors=Strausberg RL, Feingold EA, Grouse LH, etal|title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences|journal=Proc. Natl. Acad. Sci. U.S.A.|volume=99|issue=26|pages=16899–903|year=2003|pmid=12477932|doi=10.1073/pnas.242603899|pmc=139241|bibcode=2002PNAS...9916899M |doi-access=free}}
• {{cite journal|vauthors=Abu M, Waters TR|title=The main role of human thymine-DNA glycosylase is removal of thymine produced by deamination of 5-methylcytosine and not removal of ethenocytosine|journal=J. Biol. Chem.|volume=278|issue=10|pages=8739–44|year=2003|pmid=12493755|doi=10.1074/jbc.M211084200|doi-access=free}}
• {{cite journal|vauthors=Shimizu Y, Iwai S, Hanaoka F, Sugasawa K|title=Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase|journal=EMBO J.|volume=22|issue=1|pages=164–73|year=2003|pmid=12505994|doi=10.1093/emboj/cdg016|pmc=140069}}
• {{cite journal|vauthors=Chen D, Lucey MJ, Phoenix F, etal|title=T:G mismatch-specific thymine-DNA glycosylase potentiates transcription of estrogen-regulated genes through direct interaction with estrogen receptor alpha|journal=J. Biol. Chem.|volume=278|issue=40|pages=38586–92|year=2003|pmid=12874288|doi=10.1074/jbc.M304286200|doi-access=free}}
• {{cite journal|vauthors=Lehner B, Semple JI, Brown SE, etal|title=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|journal=Genomics|volume=83|issue=1|pages=153–67|year=2004|pmid=14667819|doi=10.1016/S0888-7543(03)00235-0}}
• {{cite journal|vauthors=Brandenberger R, Wei H, Zhang S, etal|title=Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation|journal=Nat. Biotechnol.|volume=22|issue=6|pages=707–16|year=2005|pmid=15146197|doi=10.1038/nbt971|s2cid=27764390}}
• {{cite journal|vauthors=Krześniak M, Butkiewicz D, Samojedny A, etal|title=Polymorphisms in TDG and MGMT genes - epidemiological and functional study in lung cancer patients from Poland|journal=Ann. Hum. Genet.|volume=68|issue=Pt 4|pages=300–12|year=2005|pmid=15225156|doi=10.1046/j.1529-8817.2004.00079.x|s2cid=35293833}}
• {{cite journal|vauthors=He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L, Sun Y, Li X, Dai Q, Song CX, Zhang K, He C, Xu GL|title=Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA.|journal=Science|volume=333|issue=6047|pages=1303–7|date=September 2011|pmid=21817016|pmc=3462231|doi=10.1126/science.1210944|bibcode=2011Sci...333.1303H}}
• {{cite journal|vauthors=Zhang L, Lu X, Lu J, Liang H, Dai Q, Xu GL, Luo C, Jiang H, He C|title=Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA.|journal=Nature Chemical Biology|volume=8|issue=4|pages=328–30|date=February 2012|pmid=22327402|pmc=3307914|doi=10.1038/nchembio.914}}
• {{Cite journal|vauthors=Xu J, Cortellino S, Tricarico R, Chang WC, Scher G, Devarajan K, Slifker M, Moore R, Bassi MR, Caretti E, Clapper M, Cooper H, Bellacosa A|date=September 2017|title=Thymine DNA Glycosylase (TDG) is involved in the pathogenesis of intestinal tumors with reduced APC expression.|journal=Oncotarget|volume=8|issue=52|pages=89988–89997|doi=10.18632/oncotarget.21219|pmc=5685726|pmid=29163805}}{{refend}}

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Category:EC 3.2.2