Figure 3.
Dynamics of adenine methylation. Adenine (A) gets methylated by the addition of CH3 (methyl) group at N6 position by DNA adenine methyltransferases 1, the writer, generating N6-methyladenine (6-mA). SeqA protein, the reader, specifically binds to hemimethylated 6-mA DNA. The 6-mA gets hydroxylated (–OH) by AlkB oxidase to N6-hydroxymethylcytosine (6-hmA). Due to the erasers like DNA 6-mA demethylase (DMAD) or N6-methyladenine demethylase-1 (NMAD1), 6-mA gets deaminated back to Adenine. 6-hmA gets demethylated indirectly to Adenine by AlkB oxidase via N6-hydroxymethyl adenine (6-hmA) and N6-formyladenine (6-fA). Adenine may also get methyl adduct to N1-methyladenine (1-mA) by environmental/endogenous alkylating agents. Similarly, 1-mA may also get demethylated indirectly by AlkB oxidase to Adenine via N1-hydroxymethyl adenine (1-hmA). AlkB is one of the prototypic oxidative dealkylation DNA repair enzymes/dioxygenases involved in the removal of alkyl adducts from DNA base by oxidative dealkylation (Redrawn from Kumar et al., 2018).