G/T mismatch-specific thymine DNA glycosylase is an enzyme that in humans is encoded by the TDG gene. [4] [5] [6] Several bacterial proteins have strong sequence homology with this protein. [7]
G/T mismatch-specific thymine DNA glycosylase is an enzyme that in humans is encoded by the TDG gene. [4] [5] [6] Several bacterial proteins have strong sequence homology with this protein. [7]
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. [6]
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. [8] 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. [9]
Thymine-DNA glycosylase has been shown to interact with:
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases.
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.
DNA replication licensing factor MCM6 is a protein that in humans is encoded by the MCM6 gene. MCM6 is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication.
Transcription factor E2F1 is a protein that in humans is encoded by the E2F1 gene.
Nuclear receptor-interacting protein 1 (NRIP1) also known as receptor-interacting protein 140 (RIP140) is a protein that in humans is encoded by the NRIP1 gene.
Small ubiquitin-related modifier 2 is a protein that in humans is encoded by the SUMO2 gene.
E3 SUMO-protein ligase PIAS4 is one of several protein inhibitor of activated STAT (PIAS) proteins. It is also known as protein inhibitor of activated STAT protein gamma, and is an enzyme that in humans is encoded by the PIAS4 gene.
Nuclear transcription factor Y subunit beta is a protein that in humans is encoded by the NFYB gene.
Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is not expressed in Bloom syndrome.
E3 SUMO-protein ligase PIAS2 is an enzyme that in humans is encoded by the PIAS2 gene.
Cyclin-O is a protein that in humans is encoded by the CCNO gene.
Small ubiquitin-related modifier 3 is a protein that in humans is encoded by the SUMO3 gene.
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.
Endonuclease VIII-like 2 is an enzyme that in humans is encoded by the NEIL2 gene.
Single-strand selective monofunctional uracil DNA glycosylase is an enzyme that in humans is encoded by the SMUG1 gene. SMUG1 is a glycosylase that removes uracil from single- and double-stranded DNA in nuclear chromatin, thus contributing to base excision repair.
Protein reversionless 3-like (REV3L) also known as DNA polymerase zeta catalytic subunit (POLZ) is an enzyme that in humans is encoded by the REV3L gene.
Cbp/p300-interacting transactivator 1 is a protein that in humans is encoded by the CITED1 gene.
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