A method for cleaving of DNA at very specific sequences. The site of cleavage is able to bind a specific protein, e.g. the lac repressor, that already contains a restriction site or is engineered to contain one; the presence of the DNA-binding protein protects the restriction site while the rest of the DNA is enzymically methylated, thus eliminating all unprotected restriction sites. Upon removal of the binding protein, the DNA can be cleaved at the one remaining restriction site.