[Frontiers in Bioscience 17, 2122-2139, June 1, 2012]

Mechanistic insight into Type I restriction endonucleases

James Youell1, Keith Firman2

1IBBS Biophysics Laboratories, School of Biological Sciences, University of Portsmouth, St. Michael's Building, White Swan Road, Portsmouth PO1 2DT, Hampshire, United Kingdom, 2Now retired from School of Biological Sciences, University of Portsmouth, King Henry Building, King Henry I Street, Portsmouth PO1 2DY, Hampshire, United Kingdom


1. Abstract
2. Introduction
2.1. Genetic organization and nomenclature
2.2. Families of Type I restriction enzymes
2.3. DNA methylation and cleavage
3. DNA translocation and molecular motor activity
3.1. Studies of DNA translocation using the Type IA R-M enzymes
3.2. Studies of DNA translocation with the Type IC R-M enzyme EcoR124I
4. DNA translocation as a Helicase-like activity
5. Mechanisms for controlling restriction activity
5.1. Subunit assembly and control of restriction and modification
5.2. Restriction alleviation and Type I restriction-modification systems
6. Cellular localization and subunit assembly
7. Perspective
8. Overall summary
9. References


Restriction and modification are two opposing activities that are used to protect bacteria from cellular invasion by DNA (e.g. bacteriophage infection). Restriction activity involves cleavage of the DNA; while modification activity is the mechanism used to "mark" host DNA and involves DNA methylation. The study of Type I restriction enzymes has often been seen as an esoteric exercise and this reflects some of their more unusual properties - non-stoichiometric (non-catalytic) cleavage of the DNA substrate, random cleavage of DNA, a massive ATPase activity, and the ability to both cleave DNA and methylate DNA. Yet these enzymes have been found in many bacteria and are very efficient as a means of protecting bacteria against bacteriophage infection, indicating they are successful enzymes. In this review, we summarise recent work on the mechanisms of action, describe switching of function and review their mechanism of action. We also discuss structural rearrangements and cellular localisation, which provide powerful mechanisms for controlling the enzyme activity. Finally, we speculate as to their involvement in recombination and discuss their relationship to helicase enzymes.