|, hThymine-DNA glycosylase, thymine DNA glycosylase|
G/T mismatch-specific thymine DNA glycosylase is an enzyme that in humans is encoded by the TDG gene.Several bacterial proteins have strong sequence homology with this protein.
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.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.
Thymine-DNA glycosylase has been shown to interact with:
Click on genes, proteins and metabolites below to link to respective 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 (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 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.
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Small ubiquitin-related modifier 2 is a protein that in humans is encoded by the SUMO2 gene.
Nuclear transcription factor Y subunit beta is a protein that in humans is encoded by the NFYB gene.
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E3 SUMO-protein ligase PIAS1 is an enzyme that in humans is encoded by the PIAS1 gene.
FACT complex subunit SSRP1 also known as structure specific recognition protein 1 is a protein that in humans is encoded by the SSRP1 gene.
Scaffold attachment factor B, also known as SAFB, is a gene with homologs that have been studied in humans and mice.
Nuclear receptor coactivator 6 is a protein that in humans is encoded by the NCOA6 gene.
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Endonuclease III-like protein 1 is an enzyme that in humans is encoded by the NTHL1 gene.
Methyl-CpG-binding domain protein 4 is a protein that in humans is encoded by the MBD4 gene.
Heat shock factor protein 2 is a protein that in humans is encoded by the HSF2 gene.
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Mitogen-activated protein kinase 11 is an enzyme that in humans is encoded by the MAPK11 gene.