(Copied and modified from Shen et al. and Stoddard (2011) Nucleic Acids Research 39 (18): 8223 – 36).

“Bacterial restriction of phage infection is dependent upon the action of restriction endonucleases (REase) that cleave individual target sites found in invading foreign DNA.  Canonical R-M systems consist of a restriction endonuclease (REase) that recognizes and cleaves an unmodified nucleotide sequence, and a cognate DNA methyltransferase (MTase) that protects the host DNA from cleavage by methylating an adenine or cytosine nucleotide base within its recognition sequence. The REase cuts unmethylated DNA targets, but not hemimethylated (the substrate that is transiently generated during DNA replication) or fully methylated DNA.

The genes that encode various components of R-M systems are found in virtually all sequenced bacterial and archaeal genomes.  Many bacteria contain multiple R-M systems and display the ability to switch between different systems and DNA specificities depending upon conditions.  The total number of R-M systems encoded in various bacterial species varies widely, ranging from single R-M genes in some bacteria to at least twenty in Helicobacter pylori.  R-M systems are extremely diverse with respect to their protein subunit composition, the length and symmetry of their DNA recognition sites, the position and pattern of DNA cleavage, requirements for various cofactors (such as divalent metal ions, ATP and S-adenosylmethionine (SAM)) and methylation status. 

The extraordinary diversity in R-M architecture and DNA recognition patterns has lead to a classification system divided into at least four distinct categories. The best studied of these are the Type II R-M systems, which usually consist of separate MTase and REase enzymes that independently recognize identical DNA sequences that are four to eight base pairs (bp) in length; many of their target sites are palindromic. Most REases of this Type IIP subclass combine their DNA recognition and cleavage functions into a single folded protein domain, which dimerizes to recognize palindromic sequences. Variations in this organization are often observed.  For example, Type IIS restriction endonucleases contain separate independently folded target recognition domains (TRDs) and nuclease domains.

An evolutionary weakness of R-M systems that comprise separate REase and MTase proteins is that they may not be able to rapidly alter their target site specificity: a change in REase specificity at even a single base pair, without an equivalent change in DNA recognition by the cognate methyltransferase would generally result in host toxicity.  One solution to this problem is to have the REase domain relinquish its own specificity determinant and directly couple its DNA recognition function to that of its corresponding MTase, which is observed for the multi-subunit type I and III R-M systems.”

Back to Top