Thymine-DNA glycosylase

Last updated
TDG
Protein TDG PDB 1wyw.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases TDG , hThymine-DNA glycosylase, thymine DNA glycosylase
External IDs OMIM: 601423 MGI: 3645587 HomoloGene: 2415 GeneCards: TDG
Gene location (Human)
Ideogram human chromosome 12.svg
Chr. Chromosome 12 (human) [1]
Human chromosome 12 ideogram.svg
HSR 1996 II 3.5e.svg
Red rectangle 2x18.png
Band 12q23.3Start103,965,822 bp [1]
End103,988,874 bp [1]
RNA expression pattern
PBB GE TDG 203743 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 Mb Chr 15: 82.52 – 82.52 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

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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Thymine-DNA glycosylase 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 articlego to article
|{{{bSize}}}px|alt=Fluorouracil (5-FU) Activity edit]]
Fluorouracil (5-FU) Activity edit
  1. The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

Related Research Articles

DNA glycosylases are a family of enzymes involved in base excision repair, classified under EC number EC 3.2.2. Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. DNA glycosylases catalyze the first step of this process. They remove the damaged nitrogenous base while leaving the sugar-phosphate backbone intact, creating an apurinic/apyrimidinic site, commonly referred to as an AP site. This is accomplished by flipping the damaged base out of the double helix followed by cleavage of the N-glycosidic bond.

Base excision repair DNA repair process

Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky helix-distorting lesions. BER is important for removing damaged bases that could otherwise cause mutations by mispairing or lead to breaks in DNA during replication. BER is initiated by DNA glycosylases, which recognize and remove specific damaged or inappropriate bases, forming AP sites. These are then cleaved by an AP endonuclease. The resulting single-strand break can then be processed by either short-patch or long-patch BER.

Werner syndrome helicase protein-coding gene in the species Homo sapiens

Werner syndrome ATP-dependent helicase, also known as DNA helicase, RecQ-like type 3, is an enzyme that in humans is encoded by the WRN gene. WRN is a member of the RecQ Helicase family. Helicase enzymes generally unwind and separate double-stranded DNA. These activities are necessary before DNA can be copied in preparation for cell division. Helicase enzymes are also critical for making a blueprint of a gene for protein production, a process called transcription. Further evidence suggests that Werner protein plays a critical role in repairing DNA. Overall, this protein helps maintain the structure and integrity of a person's DNA.

Estrogen receptor alpha protein-coding gene in the species Homo sapiens

Estrogen receptor alpha (ERα), also known as NR3A1, is one of two main types of estrogen receptor, a nuclear receptor that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ESR1.

UBE2I protein-coding gene in the species Homo sapiens

SUMO-conjugating enzyme UBC9 is an enzyme that in humans is encoded by the UBE2I gene. It is also sometimes referred to as "ubiquitin conjugating enzyme E2I" or "ubiquitin carrier protein 9", even though these names do not accurately describe its function.

ATF1 protein-coding gene in the species Homo sapiens

Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.

SUMO2 protein-coding gene in the species Homo sapiens

Small ubiquitin-related modifier 2 is a protein that in humans is encoded by the SUMO2 gene.

NFYB protein-coding gene in the species Homo sapiens

Nuclear transcription factor Y subunit beta is a protein that in humans is encoded by the NFYB gene.

ATF6 protein-coding gene in the species Homo sapiens

Activating transcription factor 6, also known as ATF6, is a protein that, in humans, is encoded by the ATF6 gene and is involved in the unfolded protein response.

PIAS1 protein-coding gene in the species Homo sapiens

E3 SUMO-protein ligase PIAS1 is an enzyme that in humans is encoded by the PIAS1 gene.

Protein inhibitor of activated STAT2 protein-coding gene in the species Homo sapiens

E3 SUMO-protein ligase PIAS2 is an enzyme that in humans is encoded by the PIAS2 gene.

Structure specific recognition protein 1 protein-coding gene in the species Homo sapiens

FACT complex subunit SSRP1 also known as structure specific recognition protein 1 is a protein that in humans is encoded by the SSRP1 gene.

SAFB protein-coding gene in the species Homo sapiens

Scaffold attachment factor B, also known as SAFB, is a gene with homologs that have been studied in humans and mice.

SUMO3 protein-coding gene in the species Homo sapiens

Small ubiquitin-related modifier 3 is a protein that in humans is encoded by the SUMO3 gene.

NTHL1 protein-coding gene in the species Homo sapiens

Endonuclease III-like protein 1 is an enzyme that in humans is encoded by the NTHL1 gene.

RBBP8 protein-coding gene in the species Homo sapiens

Retinoblastoma-binding protein 8 is a protein that in humans is encoded by the RBBP8 gene.

MBD4 protein-coding gene in the species Homo sapiens

Methyl-CpG-binding domain protein 4 is a protein that in humans is encoded by the MBD4 gene.

HSF2 protein-coding gene in the species Homo sapiens

Heat shock factor protein 2 is a protein that in humans is encoded by the HSF2 gene.

NEIL2 gene of the species Homo sapiens

Endonuclease VIII-like 2 is an enzyme that in humans is encoded by the NEIL2 gene.

CITED1 protein-coding gene in the species Homo sapiens

Cbp/p300-interacting transactivator 1 is a protein that in humans is encoded by the CITED1 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000139372 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 "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. S2CID   4235485.
  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. 1 2 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