DNA Restriction and Modification

In the mid-twentieth century it was shown that the infectivity of a bacteriophage could be determined by the host strain in which it had been propagated. A common basis for this “host-controlled” effect was shown to be the modification of DNA by methylation of defined bases within target sequences. In the absence of this strain-specific modification, DNA can be recognised as foreign and cleaved by a resident restriction endonuclease. Together restriction endonucleases and their cognate methyltransferases constitute classical Restriction-Modification (R-M) systems (Types I-III). In contrast, some restriction endonucleases (Type IV) only cut DNA when the target sequences are modified. The wide variety of systems is surveyed in this article. Restriction endonucleases were fundamental to the development of molecular biology, specifically through their application to gene cloning and DNA sequencing. Significant understanding of the molecular interactions of restriction endonucleases and methyltransferases with DNA has been achieved. The diverse nature and extensive distribution of R-M systems within bacteria and Archaea raises interest in their biological relevance to the organisms that specify them. Many bacteria encode one or two systems, some contain genes for more than 20 different systems, while the genomes of others, often intracellular parasites, do not encode homologues of any known restriction enzymes. Although the recognition of unmodified target sequences may serve to protect bacteria against phage infection, foreign DNA fragments produced by restriction can act as substrates for genetic recombination in vivo and may facilitate horizontal gene transfer.