TABLE 4.

Processivity values for DNMT3A dimer and tetramer interface mutants

Disruption of either the dimer or tetramer interface eliminated processivity in DNMT3A as observed on two different substrates. The addition of DNMT3L restored processivity in mutants that become heterotetrameric; heterodimers still had a large reduction in processivity. Values were determined by modeling as described above in the “Experimental Procedures.”

	k	koff	p	n½
	h−1	h−1
poly-dIdC
Wild type	11 ± 0.8	0.3 ± 0.0	0.98	30 ± 6.2
H873A	4.8 ± 0.1	1.7 ± 0.1	0.76	2.4 ± 1.3
H873R	1.7 ± 0.3	1.1 ± 0.3	0.62	1.4 ± 1.0
W860A	2.7 ± 0.8	1.1 ± 0.5	0.71	2.0 ± 1.2
N879A	4.7 ± 0.6	1.7 ± 0.3	0.75	2.4 ± 1.3
D876G	4.0 ± 0.3	1.0 ± 0.2	0.83	3.8 ± 1.5
R882H	5.6 ± 0.5	2.1 ± 0.2	0.73	2.2 ± 1.5
RASSF1A
Wild type	5.1 ± 0.5	0.2 ± 0.1	0.96	16 ± 5.0
H873A	3.4 ± 0.4	1.7 ± 0.2	0.66	1.7 ± 0.5
H873R	1.4 ± 0.5	1.6 ± 0.8	0.47	0.9 ± 0.4
W860A	0.8 ± 0.1	1.2 ± 0.2	0.46	0.9 ± 0.3
N879A	2.7 ± 0.3	1.0 ± 0.2	0.72	2.1 ± 0.5
D876G	2.1 ± 0.3	0.8 ± 0.3	0.69	2.1 ± 0.7
R882H	3.9 ± 0.3	1.7 ± 0.2	0.72	1.9 ± 0.3
WT + 3L	18 ± 0.3	0.1 ± 0.0	1.00	154 ± 45
H873A + 3L	10 ± 0.7	1.2 ± 0.2	0.90	6.4 ± 2.2
R882H + 3L	15 ± 0.4	0.3 ± 0.1	0.98	54 ± 8.6
R729W + 3L	20 ± 0.9	0.1 ± 0.1	0.99	132 ± 35