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. 2012 Jun 21;287(37):30941–30951. doi: 10.1074/jbc.M112.366625

FIGURE 6.

FIGURE 6.

DNMT3L and the formation of heterotetramers restores processivity to R882H DNMT3A. A, the EMSA shows that DNMT3L binds to DNMT3A tetramers to form heterotetramers. R882H binds to DNMT3L; all other mutants at the dimer interface become heterodimers. B, DNMT3L (1:1 ratio) activates DNMT3A tetramers at ∼5-fold. Dimer interface mutants show a 2–4-fold activation other than R882H, which show an 8.8-fold stimulation. DNMT3A heterotetramers (C, WT; D, R882H) are processive, and heterodimers (E, H873A) are non-processive as demonstrated by the processive chase assay. ●, only substrate (20 μm bp RASSF1A); ■, substrate and then 400 μm bp chase (pCpGL at 20 min; ▴, substrate and pCpGL at the start of the reaction.