One of the most important developments in the recent history of biochemistry is the discovery of restriction endonucleases (also called restriction enzymes). Restriction endonucleases are enzymes that catalyze the double-strand cleavage of DNA at specific base sequences. That is, restriction enzymes cut DNA strands at specific DNA sequences, generating fragments of specific sizes that can be separated and visualized on gel electrophoresis (Figure 25.6).

Restriction enzymes are widespread among bacteria as part of a defense system called restriction-modification. Typically these systems are composed of a gene that encodes a methylase that methylates a specific, short DNA sequence. This same sequence is recognized by the restriction enzyme, but the enyzme is inhibited from cutting by the methyl group. Invading viruses, however, have no such methyl group and are cut by the restriction enzyme. Thus, restriction-modification cleaves only invading DNA from outside, not the cell's own DNA. Occasionally, however, a virus manages to invade and be modified by the methylase before the restriction enzyme can act. When this happens, the virus is not blocked by the restriction-modification system of the host bacterium and can infect with a much higher frequency (Figure 25.5).