Table 1.

Some salient features of R–M enzymes (Based on Bickle and Kruger, 1993; Loenen et al., 2014).

R–M Type	MTase composition	RE composition	Mode of function
I	Complex consisting of one sequence-specific DNA-binding subunit and two MTase subunits.	Complex consisting of one sequence-specific DNA-binding subunit, two MTase and two RE subunits.	Hemimethylated DNA is preferentially methylated relative to unmethylated DNA. ATP-powered translocation of unmethylated DNA precedes double-strand cleavage at random and distant sites from the initial binding site. Methylation and cleavage of DNA are mutually exclusive.
II	Single polypeptide chain with sequence-specific DNA binding and methylation activities.	Single polypeptide chain with sequence-specific DNA binding and cleavage activities. May or may not dimerize.	Methylation and cleavage of DNA are independent reactions. DNA cleavage occurs either within the recognition site, or sometimes at a fixed distance away from the site.
III	Single polypeptide chain that can carry out sequence-specific DNA binding and methylation activities.	Complex consisting of two restriction and two modification subunits.	Methylation and DNA cleavage reactions occur simultaneously. Translocation of DNA is driven by ATP hydrolysis. DNA cleavage occurs at a fixed distance on one side of the recognition site, and only when unmethylated recognition sites are inversely oriented. Methylation has no specific requirements as to the number and orientation of sites.
IV	Not relevant.	Complex is variable, containing one (Mrr, McrA) or two (McrBC) kinds of subunits.	Double-stranded cleavage of modified DNA is preceded by GTP hydrolysis-driven DNA translocation, and occurs at sites away from the recognition sequence.