Thymine-DNA glycosylase

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Thymine-DNA glycosylase
Protein TDG PDB 1wyw.png
PDB rendering based on 1wyw.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbol TDG
External IDs OMIM601423 HomoloGene2415 GeneCards: TDG Gene
EC number 3.2.2.29
RNA expression pattern
PBB GE TDG 203743 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 6996 21665
Ensembl ENSG00000139372 ENSMUSG00000034674
UniProt Q13569 P56581
RefSeq (mRNA) NM_001008411 NM_011561
RefSeq (protein) NP_003202 NP_035691
Location (UCSC) Chr 12:
104.36 – 104.38 Mb
Chr 10:
82.63 – 82.65 Mb
PubMed search [1] [2]

G/T mismatch-specific thymine DNA glycosylase is an enzyme that in humans is encoded by the TDG gene.[1][2][3] Several bacterial proteins have strong sequence homology with this protein.[4]

Function[edit]

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]

Additionally, in 2011, the human thymine DNA glycosylase (hTDG) was reported to efficiently excises 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), the key oxidation products of 5-methylcytosine in genomic DNA.[5] 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.[6]

Interactions[edit]

Thymine-DNA glycosylase has been shown to interact with:

Interactive pathway map[edit]

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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FluoropyrimidineActivity_WP1601 go to article go to article go to article go to pathway article go to pathway article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to PubChem Compound go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to pathway article go to pathway article go to article go to article go to article go to article go to article go to WikiPathways go to article go to article go to article go to article go to article go to article go to article go to article go to article
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FluoropyrimidineActivity_WP1601 go to article go to article go to article go to pathway article go to pathway article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to PubChem Compound go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to pathway article go to pathway article go to article go to article go to article go to article go to article go to WikiPathways go to article go to article go to article go to article go to article go to article go to article go to article go to article
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Fluorouracil (5-FU) Activity edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601". 

References[edit]

  1. ^ Neddermann P, Gallinari P, Lettieri T, Schmid D, Truong O, Hsuan JJ, Wiebauer K, Jiricny J (August 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. 
  2. ^ Sard L, Tornielli S, Gallinari P, Minoletti F, Jiricny J, Lettieri T, Pierotti MA, Sozzi G, Radice P (December 1997). "Chromosomal localizations and molecular analysis of TDG gene-related sequences". Genomics 44 (2): 222–6. doi:10.1006/geno.1997.4843. PMID 9299239. 
  3. ^ a b "Entrez Gene: TDG thymine-DNA glycosylase". 
  4. ^ Gallinari P, Jiricny J (October 1996). "A new class of uracil-DNA glycosylases related to human thymine-DNA glycosylase". Nature 383 (6602): 735–8. doi:10.1038/383735a0. PMID 8878487. 
  5. ^ 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. (September 2011). "Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA.". Science 333 (6047): 1303–7. doi:10.1126/science.1210944. PMID 21817016. 
  6. ^ Zhang L, Lu X, Lu J, Liang H, Dai Q, Xu GL, Luo C, Jiang H, He C. (February 2012). "Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA.". Nature chemical biology 8 (4): 328–30. doi:10.1038/nchembio.914. PMID 22327402. 
  7. ^ Tini M, Benecke A, Um SJ, Torchia J, Evans RM, Chambon P (February 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. 
  8. ^ Chen D, Lucey MJ, Phoenix F, Lopez-Garcia J, Hart SM, Losson R, Buluwela L, Coombes RC, Chambon P, Schär P, Ali S (October 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. 
  9. ^ Takahashi H, Hatakeyama S, Saitoh H, Nakayama KI (February 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. 280 (7): 5611–21. doi:10.1074/jbc.M408130200. PMID 15569683. 
  10. ^ a b Hardeland U, Steinacher R, Jiricny J, Schär P (March 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. 
  11. ^ Minty A, Dumont X, Kaghad M, Caput D (November 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. 275 (46): 36316–23. doi:10.1074/jbc.M004293200. PMID 10961991. 


Further reading[edit]