Thymine-DNA glycosylase

G/T mismatch-specific thymine DNA glycosylase is an enzyme that in humans is encoded by the TDG gene.[5][6][7] Several bacterial proteins have strong sequence homology with this protein.[8]

TDG
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesTDG, hThymine-DNA glycosylase, thymine DNA glycosylase
External IDsOMIM: 601423 MGI: 3645587 HomoloGene: 2415 GeneCards: TDG
Gene location (Human)
Chr.Chromosome 12 (human)[1]
Band12q23.3Start103,965,822 bp[1]
End103,988,874 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

6996

545124

Ensembl

ENSG00000139372

ENSMUSG00000047347

UniProt

Q13569

n/a

RefSeq (mRNA)

NM_001008411
NM_003211
NM_001363612

XM_006521630

RefSeq (protein)

NP_003202
NP_001350541

n/a

Location (UCSC)Chr 12: 103.97 – 103.99 MbChr 15: 82.52 – 82.52 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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.[7]

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.[9] 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.[10]

Interactions

Thymine-DNA glycosylase has been shown to interact with:

Interactive pathway map

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

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

  1. GRCh38: Ensembl release 89: ENSG00000139372 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000047347 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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.
  6. 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.
  7. "Entrez Gene: TDG thymine-DNA glycosylase".
  8. 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.
  9. 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. PMC 3462231. PMID 21817016.
  10. 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. PMC 3307914. PMID 22327402.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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

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