G/T mismatch-specific thymine DNA glycosylase is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that in humans is encoded by the TDG
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Several bacterial proteins have strong
sequence homology
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spe ...
with this protein.
Function
The protein encoded by this gene belongs to the TDG/mug
DNA glycosylase
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 st ...
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
Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by Reverse transcriptase, reverse transcription of an mRNA trans ...
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.
Interactions
Thymine-DNA glycosylase has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
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CREB-binding protein,
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Estrogen receptor alpha
Estrogen receptor alpha (ERĪ±), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein)
that is activated by the sex ...
,
*
Promyelocytic leukemia protein
Promyelocytic leukemia protein (PML) (also known as MYL, RNF71, PP8675 or TRIM19) is the protein product of the PML gene. PML protein is a tumor suppressor protein required for the assembly of a number of nuclear structures, called PML-nuclear bod ...
,
*
SUMO3
Small ubiquitin-related modifier 3 is a protein that in humans is encoded by the ''SUMO3'' gene.
Function
SUMO proteins, such as SUMO3, and ubiquitin (see MIM 191339) posttranslationally modify numerous cellular proteins and affect their metab ...
,
and
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Small ubiquitin-related modifier 1
Small ubiquitin-related modifier 1 is a protein that in humans is encoded by the ''SUMO1'' gene.
Function
This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It is a ubiquitin-like protein an ...
.
Interactive pathway map
References
Further reading
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EC 3.2.2