Fig. 1. Structure of the DNMT3A^WT–DNMT3L tetramer in complex with CGA DNA.

a Domain architecture of DNMT3A and DNMT3L with the C-terminal domains marked with arrowheads. The site for R882H mutation is marked. b DNA sequence (CGA) used for the structural study. Z, zebularine. c Ribbon representations of DNMT3A^WT–DNMT3L bound to CGA DNA and SAH, with residue R882 marked. The zebularines anchored at the two active sites are shown in expanded views, with hydrogen-bonding interactions depicted as dashed lines and Fo–Fc omit map (violet) contoured at 2.0 sigma level. The SAH molecules are shown in sphere representation. d–f Close-up views of the DNA interactions of the TRD loop (d), catalytic loop (e) and RD interface (f) of DNMT3A^WT.