Type I R-M enzymes are unusual in that the holoenzyme is multifunctional and carries out both restriction and modification activities.  Therefore, it is critical to the correct function of Type I R-M enzymes that these two opposing functions are carefully controlled (Firman et al., 2000).  Type I enzymes are able to ‘read’ the methylation status at their target recognition sequence (Yuan et al., 1975) and if the site is fully methylated (both strands methylated) then the enzyme dissociates from the site (Figure 1a).  If the site is hemi-methylated then the enzyme adopts its methylation mode and methylates the DNA at the unmethylated site (Figure 1b).  However, if the DNA is unmethylated, on both strands, then the R-M enzyme undergoes a conformational change that switches the enzyme to restriction mode and the DNA is cleaved (Figure 1c, 2 & 3).