Restriction-Modification Systems

Type I restriction enzymes were the first of this class of endonucleases to be discovered, first detected in the late fifties and then isolated in the early sixties (See Murray 2000), investigations involving these enzymes led the way towards the revolution of genetic engineering. Although they have not contributed directly to this revolution because of the random nature of DNA cleavage, they remain an important area of research mainly because of their unusual biochemical properties.

The opposing activities of restriction and modification are the two components of a bacterial defence mechanism. Restriction, or DNA cleavage, is the means by which the host bacteria prevents infection by bacterial viruses (bacteriophage). The DNA of the incoming phage is recognised as "foreign" and cleaved by a restriction endonuclease.

In vivo restriction of bacteriophage lambda by two different restriction systems.

Modification, DNA methylation, is the mechanism by which the host bacteria protects its own DNA from cleavage by the restriction endonuclease. A modification methyltransferase methylates the DNA at the same recognition sequence that the restriction endonuclease uses to bind to the DNA prior to cleavage. This activity discriminates "self" DNA from "foreign" DNA. 

The R-M system must have a means of controlling these opposing functions. Two levels of control exist for Type I R-M enzymes. The first involves the ability to discriminate the methylation status of the target DNA and thus recognise host DNA versus incoming phage DNA. The second level of control is temporal and is required when a R-M system is transferred to a new host. Modification is always observed before restriction (Prakash-Cheng & Ryu Junichi, 1993). Type I R-M systems are unusually complex and it is only recently that the mechanism of temporal control has been discovered.

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Copyright © 2006 Keith Firman
Last modified: 23-Jul-2008