HpaII will not cut sites if 2nd Cytosine of the recognition sequence CCGG is methylated by SssI methyltransferase or HpaII Methyltransferase. When the 1st cytosine of 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.