TDG (E5T5G) Rabbit mAb

Methylation of DNA at cytosine residues is a heritable, epigenetic modification that is critical for proper regulation of gene expression, genomic imprinting, and mammalian development (1,2). 5-methylcytosine is a repressive epigenetic mark established de novo by two enzymes, DNMT3A and DNMT3B, and is maintained by DNMT1 (3,4). 5-methylcytosine was originally thought to be passively depleted during DNA replication. However, subsequent studies have shown that Ten-Eleven Translocation (TET) proteins TET1, TET2, and TET3 can catalyze the oxidation of methylated cytosine to 5-hydroxymethylcytosine (5-hmC) (5). Additionally, TET proteins can further oxidize 5-hmC to form 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), both of which are excised by thymine-DNA glycosylase (TDG), effectively linking cytosine oxidation to the base excision repair pathway and supporting active cytosine demethylation (6,7). Knockout or catalytic inactivation of TDG leads to embryonic lethality, due in part to the loss of DNA methylation patterns at the promoters and enhancers of developmental genes (8,9). TDG is commonly SUMOylated at Lys330, although the exact consequence of this modification is not yet fully understood. SUMOylation has been reported to help TDG dissociate from its abasic product, thereby increasing catalytic turnover (10-12). Additional studies suggest that SUMOylation affects TDG’s cellular localization or lowers its base excision activity, allowing it to act as a ‘reader’ protein for 5-fC and 5-caC modified DNA (13-14). 1.Hermann, A. et al. (2004) Cell Mol Life Sci 61, 2571-87. 2.Turek-Plewa, J. and Jagodziński, P.P. (2005) Cell Mol Biol Lett 10, 631-47. 3.Okano, M. et al. (1999) Cell 99, 247-57. 4.Li, E. et al. (1992) Cell 69, 915-26. 5.Tahiliani, M. et al. (2009) Science 324, 930-5. 6.He, Y.F. et al. (2011) Science 333, 1303-7. 7.Ito, S. et al. (2011) Science 333, 1300-3. 8.Cortázar, D. et al. (2011) Nature 470, 419-23. 9.Cortellino, S. et al. (2011) Cell 146, 67-79. 10.Hardeland, U. et al. (2002) EMBO J 21, 1456-64. 11.Baba, D. et al. (2005) Nature 435, 979-82. 12.Baba, D. et al. (2006) J Mol Biol 359, 137-47. 13.Mohan, R.D. et al. (2007) Mol Cell Biol 27, 229-43. 14.Coey, C.T. and Drohat, A.C. (2018) Nucleic Acids Res 46, 5159-5170.