dna restriction modification enzymes


Summary: Systems consisting of two enzymes, a modification methylase and a restriction endonuclease. They are closely related in their specificity and protect the DNA of a given bacterial species. The methylase adds methyl groups to adenine or cytosine residues in the same target sequence that constitutes the restriction enzyme binding site. The methylation renders the target site resistant to restriction, thereby protecting DNA against cleavage.

Top Publications

  1. Tao T, Bourne J, Blumenthal R. A family of regulatory genes associated with type II restriction-modification systems. J Bacteriol. 1991;173:1367-75 pubmed
    ..All four members of this putative regulatory gene family have a common position relative to the endonuclease genes, suggesting a common regulatory mechanism...
  2. Kelleher J, Raleigh E. Response to UV damage by four Escherichia coli K-12 restriction systems. J Bacteriol. 1994;176:5888-96 pubmed
    ..We find that all four resident restriction systems show reduced activity following UV treatment, but not in a unified fashion; each response was genetically and physiologically distinct. Possible mechanisms are discussed. ..
  3. Knowle D, Lintner R, Touma Y, Blumenthal R. Nature of the promoter activated by C.PvuII, an unusual regulatory protein conserved among restriction-modification systems. J Bacteriol. 2005;187:488-97 pubmed publisher
    ..This suggests that, like some other activator-dependent promoters, PpvuIICR may not require a -35 hexamer. Features of this transcription activation system suggest explanations for its broad host range...
  4. Dybvig K, Sitaraman R, French C. A family of phase-variable restriction enzymes with differing specificities generated by high-frequency gene rearrangements. Proc Natl Acad Sci U S A. 1998;95:13923-8 pubmed
    ..These data cast doubt on the prevailing paradigms that restriction systems are either selfish or function to confer protection from invasion by foreign DNA. ..
  5. Papapanagiotou I, Streeter S, Cary P, Kneale G. DNA structural deformations in the interaction of the controller protein C.AhdI with its operator sequence. Nucleic Acids Res. 2007;35:2643-50 pubmed
    ..The relative orientation of C.AhdI dimers in the tetrameric complex and the structural role of the conserved Py-A-T sequences found at the centre of C-protein-binding sites are discussed. ..
  6. Kasarjian J, Iida M, Ryu J. New restriction enzymes discovered from Escherichia coli clinical strains using a plasmid transformation method. Nucleic Acids Res. 2003;31:e22 pubmed
    ..Eco1158I, an isoschizomer of EcoBI, was also found in this study. ..
  7. Chin V, Valinluck V, Magaki S, Ryu J. KpnBI is the prototype of a new family (IE) of bacterial type I restriction-modification system. Nucleic Acids Res. 2004;32:e138 pubmed
    ..Furthermore, their identity scores to other uncharacterized putative genome type I sequences were 53% at maximum. Therefore, we propose that KpnBI is the prototype of a new 'type IE' family. ..
  8. Calisto B, Pich O, Piñol J, Fita I, Querol E, Carpena X. Crystal structure of a putative type I restriction-modification S subunit from Mycoplasma genitalium. J Mol Biol. 2005;351:749-62 pubmed
  9. Loenen W. Tracking EcoKI and DNA fifty years on: a golden story full of surprises. Nucleic Acids Res. 2003;31:7059-69 pubmed

More Information


  1. Titheradge A, King J, Ryu J, Murray N. Families of restriction enzymes: an analysis prompted by molecular and genetic data for type ID restriction and modification systems. Nucleic Acids Res. 2001;29:4195-205 pubmed
    ..Implications of family relationships are discussed and evidence is presented that extends the family affiliations identified in enteric bacteria to a wide range of other genera. ..
  2. Sekizaki T, Otani Y, Osaki M, Takamatsu D, Shimoji Y. Evidence for horizontal transfer of SsuDAT1I restriction-modification genes to the Streptococcus suis genome. J Bacteriol. 2001;183:500-11 pubmed
    ..These results suggest that the SsuDAT1I system could have been integrated into the S. suis chromosome by an illegitimate recombination mechanism. ..
  3. Liu Y, Ichige A, Kobayashi I. Regulation of the EcoRI restriction-modification system: Identification of ecoRIM gene promoters and their upstream negative regulators in the ecoRIR gene. Gene. 2007;400:140-9 pubmed
    ..Possible roles for these ecoRIM promoters and their negative regulators in the EcoRI R-M system are discussed. ..
  4. Nekrasov S, Agafonova O, Belogurova N, Delver E, Belogurov A. Plasmid-encoded antirestriction protein ArdA can discriminate between type I methyltransferase and complete restriction-modification system. J Mol Biol. 2007;365:284-97 pubmed
  5. Sawaya M, Zhu Z, Mersha F, Chan S, Dabur R, Xu S, et al. Crystal structure of the restriction-modification system control element C.Bcll and mapping of its binding site. Structure. 2005;13:1837-47 pubmed
    ..The C.Bcll-DNA model proposed suggests that DNA bending might play an important role in gene regulation, and that Glu27 and Asp31 in C.Bcll might function critically in the regulation. ..
  6. Murray N. 2001 Fred Griffith review lecture. Immigration control of DNA in bacteria: self versus non-self. Microbiology. 2002;148:3-20 pubmed
  7. McGeehan J, Streeter S, Thresh S, Ball N, Ravelli R, Kneale G. Structural analysis of the genetic switch that regulates the expression of restriction-modification genes. Nucleic Acids Res. 2008;36:4778-87 pubmed publisher
    ..Competition between Arg35 and an equivalent residue of the sigma(70) subunit of RNA polymerase for the Glu25 site underpins the switch from activation to repression of the endonuclease gene. ..
  8. Naderer M, Brust J, Knowle D, Blumenthal R. Mobility of a restriction-modification system revealed by its genetic contexts in three hosts. J Bacteriol. 2002;184:2411-9 pubmed
    ..The SptAI and SbaI genes lie between an equivalent pair of bacteriophage P4-related open reading frames, one of which is a putative integrase gene, while the PvuII genes are adjacent to a mob operon and a XerCD recombination (cer) site...
  9. Takahashi N, Naito Y, Handa N, Kobayashi I. A DNA methyltransferase can protect the genome from postdisturbance attack by a restriction-modification gene complex. J Bacteriol. 2002;184:6100-8 pubmed
    ..Dcm, therefore, can play the role of a "molecular vaccine" by defending the genome against parasitism by a restriction-modification gene complex...
  10. Sharp P, Kelleher J, Daniel A, Cowan G, Murray N. Roles of selection and recombination in the evolution of type I restriction-modification systems in enterobacteria. Proc Natl Acad Sci U S A. 1992;89:9836-40 pubmed
    ..coli strains B and K-12) is extremely high and may reflect the action of frequency-dependent selection mediated by bacteriophages. There is also evidence of lateral transfer of a short sequence between E. coli and S. typhimurium. ..
  11. Serfiotis Mitsa D, Roberts G, Cooper L, White J, Nutley M, Cooper A, et al. The Orf18 gene product from conjugative transposon Tn916 is an ArdA antirestriction protein that inhibits type I DNA restriction-modification systems. J Mol Biol. 2008;383:970-81 pubmed publisher
    ..Our results suggest that ArdA can overcome the restriction barrier following conjugation and so helps increase the spread of antibiotic resistance genes by horizontal gene transfer. ..
  12. Tock M, Dryden D. The biology of restriction and anti-restriction. Curr Opin Microbiol. 2005;8:466-72 pubmed
    ..Recently, there have been several studies that have shed light on the still developing field of restriction-modification and on the newly re-emerging field of anti-restriction. ..
  13. Gunn J, Stein D. The Neisseria gonorrhoeae S.NgoVIII restriction/modification system: a type IIs system homologous to the Haemophilus parahaemolyticus HphI restriction/modification system. Nucleic Acids Res. 1997;25:4147-52 pubmed
    ..The S.NgoVIII R-M genes are flanked by a 97 bp direct repeat that may be involved in the mobility of this R-M system...
  14. Jeltsch A. Maintenance of species identity and controlling speciation of bacteria: a new function for restriction/modification systems?. Gene. 2003;317:13-6 pubmed
  15. Kita K, Tsuda J, Kato T, Okamoto K, Yanase H, Tanaka M. Evidence of horizontal transfer of the EcoO109I restriction-modification gene to Escherichia coli chromosomal DNA. J Bacteriol. 1999;181:6822-7 pubmed
    ..coli K-12 chromosomal DNA. The sid gene of the prophage was inactivated by insertion of one copy of IS21. These findings may shed light on the horizontal transfer and stable maintenance of the R-M system. ..
  16. Sadykov M, Asami Y, Niki H, Handa N, Itaya M, Tanokura M, et al. Multiplication of a restriction-modification gene complex. Mol Microbiol. 2003;48:417-27 pubmed
    ..The multiplication ability in a bacterium with natural capacity for DNA release, uptake and transformation will be discussed in relation to spreading of RM gene -complexes. ..
  17. Purdy D, O Keeffe T, Elmore M, Herbert M, McLeod A, Bokori Brown M, et al. Conjugative transfer of clostridial shuttle vectors from Escherichia coli to Clostridium difficile through circumvention of the restriction barrier. Mol Microbiol. 2002;46:439-52 pubmed
    ..The transfer efficiencies achieved with both strains equated to between 1.0 x 10-6 and 5.5 x 10-5 transconjugants per donor...
  18. McGeehan J, Papapanagiotou I, Streeter S, Kneale G. Cooperative binding of the C.AhdI controller protein to the C/R promoter and its role in endonuclease gene expression. J Mol Biol. 2006;358:523-31 pubmed
    ..As the levels of C.AhdI increase further, binding of the second dimer competes with RNAP, thus down-regulating transcription of its own gene, and hence that of the endonuclease. ..
  19. He X, Ou H, Yu Q, Zhou X, Wu J, Liang J, et al. Analysis of a genomic island housing genes for DNA S-modification system in Streptomyces lividans 66 and its counterparts in other distantly related bacteria. Mol Microbiol. 2007;65:1034-48 pubmed
    ..Comparison of dnd clusters in the 12 bacteria strongly suggests that these dnd-bearing elements might have evolved from a common ancestor similar to plasmid-originated chromosome II of Pseudoalteromonas haloplanktis TAC125. ..
  20. Madsen A, Josephsen J. The LlaGI restriction and modification system of Lactococcus lactis W10 consists of only one single polypeptide. FEMS Microbiol Lett. 2001;200:91-6 pubmed
    ..Conceivably, the LlaGI gene is included in the operon of the plasmid replication machinery. Finally, it is proposed that LlaGI represents a variant of the type I R/M systems. ..
  21. Tyndall C, Lehnherr H, Sandmeier U, Kulik E, Bickle T. The type IC hsd loci of the enterobacteria are flanked by DNA with high homology to the phage P1 genome: implications for the evolution and spread of DNA restriction systems. Mol Microbiol. 1997;23:729-36 pubmed
    ..The significance of these results for the evolution of DNA restriction and modification systems is discussed...
  22. Obarska A, Blundell A, Feder M, Vejsadová S, Sisáková E, Weiserová M, et al. Structural model for the multisubunit Type IC restriction-modification DNA methyltransferase M.EcoR124I in complex with DNA. Nucleic Acids Res. 2006;34:1992-2005 pubmed
    ..The model structure, together with location of the mutant residues, provides a better background on which to study protein-protein and protein-DNA interactions in Type I R-M systems. ..
  23. Cesnaviciene E, Mitkaite G, Stankevicius K, Janulaitis A, Lubys A. Esp1396I restriction-modification system: structural organization and mode of regulation. Nucleic Acids Res. 2003;31:743-9 pubmed
    ..Our data indicate that C protein from Esp1396I RM system activates the expression of the Enase gene, which is co-transcribed from the promoter of regulatory gene, by the mechanism of coupled translation...
  24. Kobayashi I. Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution. Nucleic Acids Res. 2001;29:3742-56 pubmed
    ..The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and function of RM enzymes. ..
  25. Weiserova M, Firman K. Isolation of a non-classical mutant of the DNA recognition subunit of the type I restriction endonuclease R.EcoR124I. Biol Chem. 1998;379:585-9 pubmed
  26. O Driscoll J, Glynn F, Cahalane O, O Connell Motherway M, Fitzgerald G, van Sinderen D. Lactococcal plasmid pNP40 encodes a novel, temperature-sensitive restriction-modification system. Appl Environ Microbiol. 2004;70:5546-56 pubmed
    ..This was substantiated by use of a LlaJI promoter-lacZ fusion, which further revealed that the LlaJI operon appears to be subject to transcriptional regulation by an as yet unidentified element(s) encoded by pNP40. ..
  27. Mruk I, Rajesh P, Blumenthal R. Regulatory circuit based on autogenous activation-repression: roles of C-boxes and spacer sequences in control of the PvuII restriction-modification system. Nucleic Acids Res. 2007;35:6935-52 pubmed
    ..Any changes in that spacer reduced the stability of C.PvuII-operator complexes and abolished activation...
  28. Zhao F, Zhang X, Liang C, Wu J, Bao Q, Qin S. Genome-wide analysis of restriction-modification system in unicellular and filamentous cyanobacteria. Physiol Genomics. 2006;24:181-90 pubmed
    ..Sites and genes identified here to have been under positive selection would provide targets for further research on their structural and functional evaluations. ..
  29. Streeter S, Papapanagiotou I, McGeehan J, Kneale G. DNA footprinting and biophysical characterization of the controller protein C.AhdI suggests the basis of a genetic switch. Nucleic Acids Res. 2004;32:6445-53 pubmed
    ..Moreover, the structure and location of the C.AhdI binding site with respect to the putative -35 box preceding the C-gene suggests a possible mechanism for autoregulation of C.AhdI expression. ..
  30. McGeehan J, Streeter S, Papapanagiotou I, Fox G, Kneale G. High-resolution crystal structure of the restriction-modification controller protein C.AhdI from Aeromonas hydrophila. J Mol Biol. 2005;346:689-701 pubmed
    ..Comparison with the structure of the lambda cI ternary complex suggests that C.AhdI activates transcription through direct contact with the sigma70 subunit of RNA polymerase. ..
  31. Schouler C, Gautier M, Ehrlich S, Chopin M. Combinational variation of restriction modification specificities in Lactococcus lactis. Mol Microbiol. 1998;28:169-78 pubmed
    ..Such combinational variation of type I R-M systems may facilitate the evolution of their specificity and thus reinforce bacterial resistance against invasive foreign unmethylated DNA...
  32. Berndt C, Meier P, Wackernagel W. DNA restriction is a barrier to natural transformation in Pseudomonas stutzeri JM300. Microbiology. 2003;149:895-901 pubmed
    ..Restriction as a barrier to transformation apparently contributes to sexual isolation and therefore may promote speciation in the highly diverse species P. stutzeri. ..
  33. Miller W, Pearson B, Wells J, Parker C, Kapitonov V, Mandrell R. Diversity within the Campylobacter jejuni type I restriction-modification loci. Microbiology. 2005;151:337-51 pubmed
    ..jejuni hsd loci are presumably the result of such recombination. The importance of these findings with regard to the evolution of C. jejuni type I R-M systems is discussed. ..
  34. King G, Murray N. Restriction alleviation and modification enhancement by the Rac prophage of Escherichia coli K-12. Mol Microbiol. 1995;16:769-77 pubmed
    ..A comparison of the predicted amino acid sequences of Lar and RaI shows only a 25% identity, but a few short regions do align and may indicate residues important for structure and/or function. ..
  35. Kriukiene E, Lubiene J, Lagunavicius A, Lubys A. MnlI--The member of H-N-H subtype of Type IIS restriction endonucleases. Biochim Biophys Acta. 2005;1751:194-204 pubmed
    ..We interpret the presented experimental evidence as a suggestion that the motif 306Rx3ExHHx14Nx8H represents the active site of MnlI. Consequentially, MnlI seems to be the member of Type IIS with the active site of the H-N-H type. ..
  36. O Driscoll J, Fitzgerald G, van Sinderen D. A dichotomous epigenetic mechanism governs expression of the LlaJI restriction/modification system. Mol Microbiol. 2005;57:1532-44 pubmed
    ..LlaJI, which serves to regulate expression of the LlaJI operon. This regulatory system therefore represents the amalgamation of an epigenetic stimulation coupled to the formation of a MTase/repressor:promoter complex. ..
  37. Husain F, Tang K, Veeranagouda Y, Boente R, Patrick S, Blakely G, et al. Novel large-scale chromosomal transfer in Bacteroides fragilis contributes to its pan-genome and rapid environmental adaptation. Microb Genom. 2017;3: pubmed publisher
    ..fragilis pan-genome, (2) allows rapid adaptation to a changing environment and (3) can confer pathogenic characteristics to host symbionts...
  38. Lee J, Kim D, Moon D, Lee J, Kim M, Lee S, et al. Prediction of bacterial proteins carrying a nuclear localization signal and nuclear targeting of HsdM from Klebsiella pneumoniae. J Microbiol. 2009;47:641-5 pubmed publisher
  39. Kobayashi I. Selfishness and death: raison d'être of restriction, recombination and mitochondria. Trends Genet. 1998;14:368-74 pubmed
    ..By extrapolation, the capacity of mitochondria to kill their host eukaryotic cell might have stabilized their initial symbiosis. ..
  40. Kong J, Jytte J, Ma G. [Cloning and structure analysis of a restriction and modification system, LlaBIII from Lactococcus lactis subsp. cremoris W56]. Sheng Wu Gong Cheng Xue Bao. 2001;17:663-8 pubmed
    ..Therefore, this polypeptide encoded by LlaBIII is a multifunctional protein possessing putative DNA recognition, methylation and restriction activities. ..
  41. Ross T, Achberger E, Braymer H. Nucleotide sequence of the McrB region of Escherichia coli K-12 and evidence for two independent translational initiation sites at the mcrB locus. J Bacteriol. 1989;171:1974-81 pubmed
    ..The 33-kDa peptide may play a regulatory role in the McrB restriction of DNA containing 5-methylcytosine. ..
  42. Styriak I, Pristas P, Javorsky P. Lack of GATC sites in the genome of Streptococcus bovis bacteriophage F4. Res Microbiol. 2000;151:285-9 pubmed
    ..The short oligonucleotide composition of available S. bovis DNA sequences suggested the existence of an unknown mechanism for counterselection of GATC sites in S. bovis bacteriophages. ..
  43. Chen P, Li J, Zhao J, He L, Zhang Z. Differential dependence on DNA ligase of type II restriction enzymes: a practical way toward ligase-free DNA automaton. Biochem Biophys Res Commun. 2007;353:733-7 pubmed
  44. Katna A, Boratynski R, Furmanek Blaszk B, Zolcinska N, Sektas M. Unbalanced restriction impairs SOS-induced DNA repair effects. J Microbiol Biotechnol. 2010;20:30-8 pubmed
    ..Our data provide further insights into the benefits and disadvantages of maintaining of a type II R-M system, highlighting its impact on host cell fitness. ..
  45. Poly F, Threadgill D, Stintzi A. Identification of Campylobacter jejuni ATCC 43431-specific genes by whole microbial genome comparisons. J Bacteriol. 2004;186:4781-95 pubmed
    ..In conclusion, this study provides a valuable resource to further investigate Campylobacter diversity and pathogenesis. ..
  46. Fox K, Srikhanta Y, Jennings M. Phase variable type III restriction-modification systems of host-adapted bacterial pathogens. Mol Microbiol. 2007;65:1375-9 pubmed
  47. Waldron D, Lindsay J. Sau1: a novel lineage-specific type I restriction-modification system that blocks horizontal gene transfer into Staphylococcus aureus and between S. aureus isolates of different lineages. J Bacteriol. 2006;188:5578-85 pubmed
    ..aureus isolates from other species, as well as for controlling the spread of resistance genes between isolates of different S. aureus lineages. Blocking Sau1 should also allow genetic manipulation of clinical strains of S. aureus. ..
  48. Mruk I, Cichowicz M, Kaczorowski T. Characterization of the LlaCI methyltransferase from Lactococcus lactis subsp. cremoris W15 provides new insights into the biology of type II restriction-modification systems. Microbiology. 2003;149:3331-41 pubmed
    ..This observation suggests that sensitivity of the M.LlaCI to Mg(2+) may strengthen the restriction activity of the cognate endonuclease in the bacterial cell. Other biological implications of this finding are also discussed. ..
  49. Lee J, Karamychev V, Kozyavkin S, Mills D, Pavlov A, Pavlova N, et al. Comparative genomic analysis of the gut bacterium Bifidobacterium longum reveals loci susceptible to deletion during pure culture growth. BMC Genomics. 2008;9:247 pubmed publisher
  50. Bahl M, Hansen L, Sørensen S. Persistence mechanisms of conjugative plasmids. Methods Mol Biol. 2009;532:73-102 pubmed publisher
    ..Finally, various molecular adaptations of plasmids to better match the genetic background of their bacterial host cell will be described. ..
  51. Smith R, Josephsen J, Szczelkun M. The single polypeptide restriction-modification enzyme LlaGI is a self-contained molecular motor that translocates DNA loops. Nucleic Acids Res. 2009;37:7219-30 pubmed publisher
    ..LlaGI is therefore an example of a polypeptide that is a completely self-contained, multi-functional molecular machine. ..
  52. Labrie S, Samson J, Moineau S. Bacteriophage resistance mechanisms. Nat Rev Microbiol. 2010;8:317-27 pubmed publisher
    ..In this Review, we highlight the most important antiviral mechanisms of bacteria as well as the counter-attacks used by phages to evade these systems. ..
  53. Willemse N, Schultsz C. Distribution of Type I Restriction-Modification Systems in Streptococcus suis: An Outlook. Pathogens. 2016;5: pubmed
    ..suis genome with population structure. We speculate on the potential role of Type I R-M systems in S. suis given the recently described associations of Type I R-M systems with virulence and propose future research directions. ..