Biology:Thymine-DNA glycosylase

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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.

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.

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 with:

• CREB-binding protein,
• Estrogen receptor alpha,
• Promyelocytic leukemia protein,
• SUMO3, and
• Small ubiquitin-related modifier 1.

Further reading

• Lindahl T (1982). "DNA repair enzymes". Annu. Rev. Biochem. 51: 61–87. doi:10.1146/annurev.bi.51.070182.000425. PMID 6287922. 
• "Thymine DNA glycosylase". Base Excision Repair. Progress in Nucleic Acid Research and Molecular Biology. 68. 2001. 235–53. doi:10.1016/S0079-6603(01)68103-0. ISBN 978-0-12-540068-8. 
• "Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun". Proc. Natl. Acad. Sci. U.S.A. 89 (13): 5789–93. 1992. doi:10.1073/pnas.89.13.5789. PMID 1631061. Bibcode: 1992PNAS...89.5789C. 
• "Efficient removal of uracil from G.U mispairs by the mismatch-specific thymine DNA glycosylase from HeLa cells". Proc. Natl. Acad. Sci. U.S.A. 91 (5): 1642–6. 1994. doi:10.1073/pnas.91.5.1642. PMID 8127859. 
• "The purification of a mismatch-specific thymine-DNA glycosylase from HeLa cells". J. Biol. Chem. 268 (28): 21218–24. 1993. doi:10.1016/S0021-9258(19)36913-3. PMID 8407958. 
• "Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatch recognition by complementary-strand interactions". Cell 92 (1): 117–29. 1998. doi:10.1016/S0092-8674(00)80904-6. PMID 9489705. 
• "The DNA glycosylase T:G mismatch-specific thymine DNA glycosylase represses thyroid transcription factor-1-activated transcription". J. Biol. Chem. 276 (36): 33569–75. 2001. doi:10.1074/jbc.M104963200. PMID 11438542. 
• "Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription". Mol. Cell 9 (2): 265–77. 2002. doi:10.1016/S1097-2765(02)00453-7. PMID 11864601. 
• "Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover". EMBO J. 21 (6): 1456–64. 2002. doi:10.1093/emboj/21.6.1456. PMID 11889051. 
• "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M. 
• "The main role of human thymine-DNA glycosylase is removal of thymine produced by deamination of 5-methylcytosine and not removal of ethenocytosine". J. Biol. Chem. 278 (10): 8739–44. 2003. doi:10.1074/jbc.M211084200. PMID 12493755. 
• "Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase". EMBO J. 22 (1): 164–73. 2003. doi:10.1093/emboj/cdg016. PMID 12505994. 
• "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. 2003. doi:10.1074/jbc.M304286200. PMID 12874288. 
• "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region". Genomics 83 (1): 153–67. 2004. doi:10.1016/S0888-7543(03)00235-0. PMID 14667819. 
• "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. 2005. doi:10.1038/nbt971. PMID 15146197. 
• "Polymorphisms in TDG and MGMT genes - epidemiological and functional study in lung cancer patients from Poland". Ann. Hum. Genet. 68 (Pt 4): 300–12. 2005. doi:10.1046/j.1529-8817.2004.00079.x. PMID 15225156. 
• "Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA.". Science 333 (6047): 1303–7. September 2011. doi:10.1126/science.1210944. PMID 21817016. Bibcode: 2011Sci...333.1303H. 
• "Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA.". Nature Chemical Biology 8 (4): 328–30. February 2012. doi:10.1038/nchembio.914. PMID 22327402. 
• "Thymine DNA Glycosylase (TDG) is involved in the pathogenesis of intestinal tumors with reduced APC expression.". Oncotarget 8 (52): 89988–89997. September 2017. doi:10.18632/oncotarget.21219. PMID 29163805.