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The obligate human pathogen\n                    <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n                    carries one of the highest loads of RMS in its genome; between 13 to 15 of the three main types. Previous work has described their organization in the reference genome FA1090 and has inferred the associated methylated motifs. Here, we studied the structure of RMS and target methylated motifs in 25 gonococcal strains sequenced with Single Molecule Real-Time (SMRT) technology, which provides data on DNA modification. The results showed a variable picture of active RMS in different strains, with phase variation switching the activity of Type III RMS, and both the activity and specificity of a Type I RMS. Interestingly, the Dam methylase was found in place of the NgoAXI endonuclease in two of the strains, despite being previously thought to be absent in the gonococcus. We also identified the real methylation target of NgoAXII as 5\u2032-GCAGA-3\u2032, different from that previously described. Results from this work give further insights into the diversity and dynamics of RMS and methylation patterns in\n                    <jats:italic>N. gonorrhoeae<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-51102-2","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T06:04:04Z","timestamp":1570773844000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Genetic variation regulates the activation and specificity of Restriction-Modification systems in Neisseria gonorrhoeae"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4162-0228","authenticated-orcid":false,"given":"Leonor","family":"S\u00e1nchez-Bus\u00f3","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0688-2521","authenticated-orcid":false,"given":"Daniel","family":"Golparian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-5958","authenticated-orcid":false,"given":"Julian","family":"Parkhill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Unemo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon R.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,11]]},"reference":[{"key":"51102_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/978-1-4939-9496-0_3","volume":"1997","author":"M Unemo","year":"2019","unstructured":"Unemo, M., Golparian, D. & Eyre, D. W. Antimicrobial resistance in Neisseria gonorrhoeae and treatment of gonorrhea. Methods Mol Biol 1997, 37\u201358, https:\/\/doi.org\/10.1007\/978-1-4939-9496-0_3 (2019).","journal-title":"Methods Mol Biol"},{"key":"51102_CR2","doi-asserted-by":"publisher","first-page":"e1000400","DOI":"10.1371\/journal.ppat.1000400","volume":"5","author":"YN Srikhanta","year":"2009","unstructured":"Srikhanta, Y. N. et al. Phasevarions mediate random switching of gene expression in pathogenic Neisseria. PLoS Pathog 5, e1000400, https:\/\/doi.org\/10.1371\/journal.ppat.1000400 (2009).","journal-title":"PLoS Pathog"},{"key":"51102_CR3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/j.1574-6968.2009.01760.x","volume":"300","author":"M Adamczyk-Poplawska","year":"2009","unstructured":"Adamczyk-Poplawska, M., Lower, M. & Piekarowicz, A. Characterization of the NgoAXP: phase-variable Type III restriction-modification system in Neisseria gonorrhoeae. FEMS Microbiol Lett 300, 25\u201335, https:\/\/doi.org\/10.1111\/j.1574-6968.2009.01760.x (2009).","journal-title":"FEMS Microbiol Lett"},{"key":"51102_CR4","doi-asserted-by":"publisher","first-page":"6750","DOI":"10.1128\/JB.05672-11","volume":"193","author":"M Adamczyk-Poplawska","year":"2011","unstructured":"Adamczyk-Poplawska, M., Lower, M. & Piekarowicz, A. Deletion of one nucleotide within the homonucleotide tract present in the hsdS gene alters the DNA sequence specificity of Type I restriction-modification system NgoAV. J Bacteriol 193, 6750\u20136759, https:\/\/doi.org\/10.1128\/JB.05672-11 (2011).","journal-title":"J Bacteriol"},{"key":"51102_CR5","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.3389\/fmicb.2015.01426","volume":"6","author":"A Kwiatek","year":"2015","unstructured":"Kwiatek, A., Mrozek, A., Bacal, P., Piekarowicz, A. & Adamczyk-Poplawska, M. Type III methyltransferase M.NgoAX from Neisseria gonorrhoeae FA1090 regulates biofilm formation and interactions with human cells. Front Microbiol 6, 1426, https:\/\/doi.org\/10.3389\/fmicb.2015.01426 (2015).","journal-title":"Front Microbiol"},{"key":"51102_CR6","doi-asserted-by":"publisher","first-page":"e1005854","DOI":"10.1371\/journal.pgen.1005854","volume":"12","author":"MJ Blow","year":"2016","unstructured":"Blow, M. J. et al. The epigenomic landscape of prokaryotes. PLoS Genet 12, e1005854, https:\/\/doi.org\/10.1371\/journal.pgen.1005854 (2016).","journal-title":"PLoS Genet"},{"key":"51102_CR7","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1146\/annurev-genet-120213-092007","volume":"48","author":"E Rotman","year":"2014","unstructured":"Rotman, E. & Seifert, H. S. The genetics of Neisseria species. 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