Contributors: Aude Bernheim, Florian Tesson


Restriction modification systems are the most abundant antiphage systems. They already have their own Wikipedia page

Molecular Mechanisms

Several reviews detail the molecular mechanisms of restriction-modification systems. For example in () :

"Bacterial restriction-modification (R-M) systems function as prokaryotic immune systems that attack foreign DNA entering the cell () . Typically, R-M systems have enzymes responsible for two opposing activities: a restriction endonuclease (REase) that recognizes a specific DNA sequence for cleavage and a cognate methyltransferase (MTase) that confers protection from cleavage by methylation of adenine or cytosine bases within the same recognition sequence. REases recognize ‘non-self’ DNA (Figure 1), such as that of phage and plasmids, by its lack of characteristic modification within specific recognition sites () . Foreign DNA is then inactivated by endonucleolytic cleavage. Generally, methylation of a specific cytosine or adenine within the recognition sequence confers protection from restriction. Host DNA is normally methylated by the MTase following replication, whereas invading non-self DNA is not."

Figure 1. The function of R-M systems, as illustrated by Type I R-M enzymes. From () .

Example of genomic structure

A total of 5 subsystems have been described for the RM system.

Here is some examples found in the RefSeq database:

The RM_Type_I system in Tessaracoccus flavescens (GCF_001998865.1, NZ_CP019607) is composed of 3 proteins Type_I_MTases (WP_237268350.1) Type_I_S (WP_077346826.1) Type_I_REases (WP_237268249.1)

The RM_Type_II system in Aeromonas caviae (GCF_000783775.2, NZ_CP026055) is composed of 2 proteins Type_II_MTases (WP_042865101.1) Type_II_REases (WP_042865102.1)

The RM_Type_IIG system in Microbacterium wangchenii (GCF_004564355.1, NZ_CP038266) is composed of 1 protein: Type_IIG (WP_135067980.1)

The RM_Type_III system in Sphingobacterium spiritivorum (GCF_016725325.1, NZ_CP068083) is composed of 2 proteins Type_III_REases (WP_139420208.1) Type_III_MTases (WP_139420206.1)

The RM_Type_IV system in Halobaculum rubrum (GCF_019880225.1, NZ_CP082284) is composed of 1 protein: Type_IV_REases (WP_222915961.1)

Distribution of the system among prokaryotes

Among the 22,803 complete genomes of RefSeq, the RM is detected in 18264 genomes (80.09 %).

The system was detected in 6137 different species.

Proportion of genome encoding the RM system for the 14 phyla with more than 50 genomes in the RefSeq database.


Experimentaly determined structure

Many structure for the different types of restriction-modification system are available on the Protein Data Bank.


Restriction modification Type I Prr

Experimental validation

Many RM systems defend against many phages, as such we cannot map this correctly.


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