The TET2 enzyme mediates the stepwise conversion of 5-methylcytosine (5mC) to 5-carboxylcytosine (5caC). Previously, our experimental and computational work identified structural differences between both single-stranded (ss) and double-stranded (ds) DNA and RNA, as well as mixed DNA-RNA substrates (Biochemistry 58 (2019) 411). TET2 was found to selectively favor double-stranded substrates over …