Type III restriction-modification enzymes: a historical perspective

Abstract

Restriction endonucleases interact with DNA at specific sites leading to cleavage of DNA. Bacterial DNA is protected from restriction endonuclease cleavage by modifying the DNA using a DNA methyltransferase. Based on their molecular structure, sequence recognition, cleavage position and cofactor requirements, restriction–modification (R–M) systems are classified into four groups. Type III R–M enzymes need to interact with two separate unmethylated DNA sequences in inversely repeated head-to-head orientations for efficient cleavage to occur at a defined location (25–27 bp downstream of one of the recognition sites). Like the Type I R–M enzymes, Type III R–M enzymes possess a sequence-specific ATPase activity for DNA cleavage. ATP hydrolysis is required for the long-distance communication between the sites before cleavage. Different models, based on 1D diffusion and/or 3D-DNA looping, exist to explain how the long-distance interaction between the two recognition sites takes place. Type III R–M systems are found in most sequenced bacteria. Genome sequencing of many pathogenic bacteria also shows the presence of a number of phase-variable Type III R–M systems, which play a role in virulence. A growing number of these enzymes are being subjected to biochemical and genetic studies, which, when combined with ongoing structural analyses, promise to provide details for mechanisms of DNA recognition and catalysis.

Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding

“…the gut of humans or the environment, as well as increase the uptake and exchange of DNA (e.g., plasmids) [69]. Moreover, ICEKp258.2 harbors a type III restriction-modification system that could serve as a ‘host specificity’ system that only allows the exchange of certain compatible plasmids [70]. These unique genetic factors may potentially contribute to the dissemination of ST258.…”

Evolutionary Genomics of Defense Systems in Archaea and Bacteria

“…The most complex, ATP-dependent type I RM systems encompass three genes that encode the R (restriction), M (modification), and S (specificity) subunits of the RMS complex; the R subunit, in addition to REase, also contains a distinct ATPase domain that belongs to helicase superfamily II (15, 99, 163). Type III RM systems resemble type II systems in that they consist of only R and M subunits, but they are similar to type I systems in that the R subunit also contains the helicase domain and the reaction is ATP dependent (19, 136). Type IV RM systems are distinct two-subunit complexes that consist of a AAA + family GTPase and an endonuclease (15, 100).…”

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

“…In their most basic form, R‐M systems are linked genes (like other prokaryotic operons), which code for a modification enzyme that covalently modifies DNA and a restriction endonuclease that cuts DNA upon recognizing specific sequence signatures 7, 10. However, R‐M systems often exhibit great diversity, and include other linked genes whose products might perform various accessory functions, such as target site recognition, DNA unwinding, long‐distance DNA‐looping and translocation, and regulation or augmentation of the restriction activity 6, 7, 10, 11, 12, 13, 14.…”