HpaII will not cut sites that have been methylated by SssI methyltransferase or HpaII Methyltransferase. When the sites have been methylated by MspI methyltransferase, the enzyme will cut 300 times slower than unmethylated DNA and 50 times slower if the DNA is hemi-methylated. McClelland, M., Nelson, M., Raschke, E. (1994). Nucleic Acids Research 22, No. 17, 3640-3659.