{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:41:39Z","timestamp":1790764899633,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","award":["CNRS-UMR 3525"],"award-info":[{"award-number":["CNRS-UMR 3525"]}],"id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jeunes Chercheurs","award":["ANR-19-CE12-0001"],"award-info":[{"award-number":["ANR-19-CE12-0001"]}]},{"name":"Laboratoires d\u2019Excellence","award":["ANR-10-LABX-62-IBEID"],"award-info":[{"award-number":["ANR-10-LABX-62-IBEID"]}]},{"DOI":"10.13039\/501100004792","name":"Minist\u00e8re de l\u2019Enseignement Sup\u00e9rieur et de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003762","name":"Institut Pasteur","doi-asserted-by":"publisher","award":["ANR-19-CE12-0001"],"award-info":[{"award-number":["ANR-19-CE12-0001"]}],"id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003762","name":"Institut Pasteur","doi-asserted-by":"publisher","award":["ANR-10-LABX-62-IBEID"],"award-info":[{"award-number":["ANR-10-LABX-62-IBEID"]}],"id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Vibrio cholerae, the pathogenic bacterium that causes cholera, has two chromosomes (Chr1, Chr2) that replicate in a well-orchestrated sequence. Chr2 initiation is triggered only after the replication of the crtS site on Chr1. The initiator of Chr2 replication, RctB, displays activities corresponding with its different binding sites: initiator at the iteron sites, repressor at the 39m sites, and trigger at the crtS site. The mechanism by which RctB relays the signal to initiate Chr2 replication from crtS is not well-understood. In this study, we provide new insights into how Chr2 replication initiation is regulated by crtS via RctB. We show that crtS (on Chr1) acts as an anti-inhibitory site by preventing 39m sites (on Chr2) from repressing initiation. The competition between these two sites for RctB binding is explained by the fact that RctB interacts with crtS and 39m via the same DNA-binding surface. We further show that the extreme C-terminal tail of RctB, essential for RctB self-interaction, is crucial for the control exerted by crtS. This subregion of RctB is conserved in all Vibrio, but absent in other Rep-like initiators. Hence, the coordinated replication of both chromosomes likely results from the acquisition of this unique domain by RctB.<\/jats:p>","DOI":"10.1093\/nar\/gkab903","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T10:21:24Z","timestamp":1632392484000},"page":"11119-11133","source":"Crossref","is-referenced-by-count":18,"title":["The coordinated replication of\n                    <i>Vibrio cholerae<\/i>\n                    \u2019s two chromosomes required the acquisition of a unique domain by the RctB initiator"],"prefix":"10.1093","volume":"49","author":[{"given":"Florian","family":"Fournes","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Unit\u00e9 Plasticit\u00e9 du G\u00e9nome Bact\u00e9rien, D\u00e9partement G\u00e9nomes et G\u00e9n\u00e9tique, Paris\u00a075015, France"},{"name":"Centre National de la Recherche Scientifique, UMR3525, Paris\u00a075015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theophile","family":"Niault","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Unit\u00e9 Plasticit\u00e9 du G\u00e9nome Bact\u00e9rien, D\u00e9partement G\u00e9nomes et G\u00e9n\u00e9tique, Paris\u00a075015, France"},{"name":"Centre National de la Recherche Scientifique, UMR3525, Paris\u00a075015, France"},{"name":"Sorbonne Universit\u00e9, Coll\u00e8ge Doctoral, Paris\u00a075005, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Czarnecki","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Unit\u00e9 Plasticit\u00e9 du G\u00e9nome Bact\u00e9rien, D\u00e9partement G\u00e9nomes et G\u00e9n\u00e9tique, Paris\u00a075015, France"},{"name":"Centre National de la Recherche Scientifique, UMR3525, Paris\u00a075015, France"},{"name":"University of Warsaw, Department of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, Warsaw\u00a002-096, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvise","family":"Tissier-Visconti","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Unit\u00e9 Plasticit\u00e9 du G\u00e9nome Bact\u00e9rien, D\u00e9partement G\u00e9nomes et G\u00e9n\u00e9tique, Paris\u00a075015, France"},{"name":"Centre National de la Recherche Scientifique, UMR3525, Paris\u00a075015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6482-6002","authenticated-orcid":false,"given":"Didier","family":"Mazel","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Unit\u00e9 Plasticit\u00e9 du G\u00e9nome Bact\u00e9rien, D\u00e9partement G\u00e9nomes et G\u00e9n\u00e9tique, Paris\u00a075015, France"},{"name":"Centre National de la Recherche Scientifique, UMR3525, Paris\u00a075015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7097-9072","authenticated-orcid":false,"given":"Marie-Eve","family":"Val","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Unit\u00e9 Plasticit\u00e9 du G\u00e9nome Bact\u00e9rien, D\u00e9partement G\u00e9nomes et G\u00e9n\u00e9tique, Paris\u00a075015, France"},{"name":"Centre National de la Recherche Scientifique, UMR3525, Paris\u00a075015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"2021110312483830700_B1","doi-asserted-by":"crossref","first-page":"e00019-17","DOI":"10.1128\/MMBR.00019-17","article-title":"The divided bacterial genome: structure, function, and evolution","volume":"81","author":"diCenzo","year":"2017","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"2021110312483830700_B2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.tim.2009.12.010","article-title":"Introducing the bacterial \u2018chromid\u2019: not a chromosome, not a plasmid","volume":"18","author":"Harrison","year":"2010","journal-title":"Trends Microbiol."},{"key":"2021110312483830700_B3","doi-asserted-by":"crossref","first-page":"a018168","DOI":"10.1101\/cshperspect.a018168","article-title":"Coevolution of the organization and structure of prokaryotic genomes","volume":"8","author":"Touchon","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2021110312483830700_B4","doi-asserted-by":"crossref","first-page":"e1000939","DOI":"10.1371\/journal.pgen.1000939","article-title":"DNA adenine methylation is required to replicate both Vibrio cholerae chromosomes once per cell cycle","volume":"6","author":"Demarre","year":"2010","journal-title":"PLos Genet."},{"key":"2021110312483830700_B5","doi-asserted-by":"crossref","first-page":"6419","DOI":"10.1128\/JB.00565-06","article-title":"Independent control of replication initiation of the two Vibrio cholerae chromosomes by DnaA and RctB","volume":"188","author":"Duigou","year":"2006","journal-title":"J. Bacteriol."},{"key":"2021110312483830700_B6","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0092-8674(03)00611-1","article-title":"Distinct replication requirements for the two Vibrio cholerae chromosomes","volume":"114","author":"Egan","year":"2003","journal-title":"Cell"},{"key":"2021110312483830700_B7","doi-asserted-by":"crossref","first-page":"11016","DOI":"10.1093\/nar\/gkaa826","article-title":"Interactions of replication initiator RctB with single- and double-stranded DNA in origin opening of Vibrio cholerae chromosome 2","volume":"48","author":"Chatterjee","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2021110312483830700_B8","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.PLAS-0026-2014","article-title":"Iteron Plasmids","volume":"2","author":"Konieczny","year":"2014","journal-title":"Microbiol. Spectr."},{"key":"2021110312483830700_B9","first-page":"3724","article-title":"The replication initiator of the cholera pathogen's second chromosome shows structural similarity to plasmid initiators","volume":"45","author":"Orlova","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2021110312483830700_B10","first-page":"10145","article-title":"Vibrio cholerae chromosome 2 copy number is controlled by the methylation-independent binding of its monomeric initiator to the chromosome 1 crtS site","volume":"46","author":"de\u00a0Lemos\u00a0Martins","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2021110312483830700_B11","doi-asserted-by":"crossref","first-page":"6026","DOI":"10.1093\/nar\/gks260","article-title":"Replication regulation of Vibrio cholerae chromosome II involves initiator binding to the origin both as monomer and as dimer","volume":"40","author":"Jha","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2021110312483830700_B12","doi-asserted-by":"crossref","first-page":"e00427-17","DOI":"10.1128\/mBio.00427-17","article-title":"The DnaK chaperone uses different mechanisms to promote and inhibit replication of Vibrio cholerae chromosome 2","volume":"8","author":"Jha","year":"2017","journal-title":"MBio"},{"key":"2021110312483830700_B13","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1073\/pnas.1013244108","article-title":"Transition from a plasmid to a chromosomal mode of replication entails additional regulators","volume":"108","author":"Venkova-Canova","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021110312483830700_B14","doi-asserted-by":"crossref","first-page":"e00033-16","DOI":"10.1128\/MMBR.00033-16","article-title":"Random versus cell cycle-regulated replication initiation in bacteria: insights from studying Vibrio cholerae chromosome 2","volume":"81","author":"Ramachandran","year":"2017","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"2021110312483830700_B15","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.3389\/fmicb.2018.01833","article-title":"Replicate Once Per Cell Cycle: Replication Control of Secondary Chromosomes","volume":"9","author":"Fournes","year":"2018","journal-title":"Front Microbiol"},{"key":"2021110312483830700_B16","doi-asserted-by":"crossref","first-page":"e1007251","DOI":"10.1371\/journal.pgen.1007251","article-title":"Synchronous termination of replication of the two chromosomes is an evolutionary selected feature in Vibrionaceae","volume":"14","author":"Kemter","year":"2018","journal-title":"PLos Genet."},{"key":"2021110312483830700_B17","doi-asserted-by":"crossref","first-page":"3124","DOI":"10.1038\/sj.emboj.7601747","article-title":"The two chromosomes of Vibrio cholerae are initiated at different time points in the cell cycle","volume":"26","author":"Rasmussen","year":"2007","journal-title":"EMBO J."},{"key":"2021110312483830700_B18","doi-asserted-by":"crossref","first-page":"e1501914","DOI":"10.1126\/sciadv.1501914","article-title":"A checkpoint control orchestrates the replication of the two chromosomes of Vibrio cholerae","volume":"2","author":"Val","year":"2016","journal-title":"Sci. Adv."},{"key":"2021110312483830700_B19","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.plasmid.2011.12.009","article-title":"A 29-mer site regulates transcription of the initiator gene as well as function of the replication origin of Vibrio cholerae chromosome II","volume":"67","author":"Venkova-Canova","year":"2012","journal-title":"Plasmid"},{"key":"2021110312483830700_B20","doi-asserted-by":"crossref","first-page":"e1004184","DOI":"10.1371\/journal.pgen.1004184","article-title":"Chromosome I controls chromosome II replication in Vibrio cholerae","volume":"10","author":"Baek","year":"2014","journal-title":"PLos Genet."},{"key":"2021110312483830700_B21","doi-asserted-by":"crossref","first-page":"12051","DOI":"10.1073\/pnas.0605120103","article-title":"Transcriptional inactivation of a regulatory site for replication of Vibrio cholerae chromosome II","volume":"103","author":"Venkova-Canova","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021110312483830700_B22","doi-asserted-by":"crossref","first-page":"10538","DOI":"10.1093\/nar\/gku771","article-title":"Initiator protein dimerization plays a key role in replication control of Vibrio cholerae chromosome 2","volume":"42","author":"Jha","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2021110312483830700_B23","doi-asserted-by":"crossref","first-page":"e1007426","DOI":"10.1371\/journal.pgen.1007426","article-title":"Chromosome 1 licenses chromosome 2 replication in Vibrio cholerae by doubling the crtS gene dosage","volume":"14","author":"Ramachandran","year":"2018","journal-title":"PLos Genet."},{"key":"2021110312483830700_B24","doi-asserted-by":"crossref","first-page":"5752","DOI":"10.1073\/pnas.95.10.5752","article-title":"A bacterial two-hybrid system based on a reconstituted signal transduction pathway","volume":"95","author":"Karimova","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021110312483830700_B25","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.bdq.2016.10.002","article-title":"Three-color crystal digital PCR","volume":"10","author":"Madic","year":"2016","journal-title":"Biomol. Detect. Quantif."},{"key":"2021110312483830700_B26","doi-asserted-by":"crossref","first-page":"e1002778","DOI":"10.1371\/journal.pgen.1002778","article-title":"The regulatory network of natural competence and transformation of Vibrio cholerae","volume":"8","author":"Lo\u00a0Scrudato","year":"2012","journal-title":"PLoS Genet."},{"key":"2021110312483830700_B27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12915-020-00777-5","article-title":"Macromolecular crowding links ribosomal protein gene dosage to growth rate in Vibrio cholerae","volume":"18","author":"Soler-Bistue","year":"2020","journal-title":"BMC Biol."},{"key":"2021110312483830700_B28","doi-asserted-by":"crossref","first-page":"7167","DOI":"10.1128\/JB.187.21.7167-7175.2005","article-title":"Multipartite regulation of rctB, the replication initiator gene of Vibrio cholerae chromosome II","volume":"187","author":"Pal","year":"2005","journal-title":"J. Bacteriol."},{"key":"2021110312483830700_B29","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"2021110312483830700_B30","article-title":"ColabFold - making protein folding accessible to all","author":"Mirdita","year":"2021"},{"key":"2021110312483830700_B31","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: structure visualization for researchers, educators, and developers","volume":"30","author":"Pettersen","year":"2021","journal-title":"Protein Sci."},{"key":"2021110312483830700_B32","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1039\/b919671d","article-title":"Helix propensities of conformationally restricted amino acids. Non-natural substitutes for helix breaking proline and helix forming alanine","volume":"8","author":"Alias","year":"2010","journal-title":"Org. Biomol. Chem."},{"key":"2021110312483830700_B33","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1111\/j.1365-2958.2007.05973.x","article-title":"Selective chromosome amplification in Vibrio cholerae","volume":"66","author":"Srivastava","year":"2007","journal-title":"Mol. Microbiol."},{"key":"2021110312483830700_B34","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.3389\/fmicb.2018.02103","article-title":"A requirement for global transcription factor Lrp in licensing replication of Vibrio cholerae chromosome 2","volume":"9","author":"Ciaccia","year":"2018","journal-title":"Front Microbiol"},{"key":"2021110312483830700_B35","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fmolb.2016.00039","article-title":"Replisome assembly at bacterial chromosomes and iteron plasmids","volume":"3","author":"Wegrzyn","year":"2016","journal-title":"Front Mol Biosci"},{"key":"2021110312483830700_B36","doi-asserted-by":"crossref","first-page":"8351","DOI":"10.1074\/jbc.M708684200","article-title":"A common mechanism for the ATP-DnaA-dependent formation of open complexes at the replication origin","volume":"283","author":"Ozaki","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2021110312483830700_B37","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s004380050294","article-title":"The localized melting of mini-F origin by the combined action of the mini-F initiator protein (RepE) and HU and DnaA of Escherichia coli","volume":"253","author":"Kawasaki","year":"1996","journal-title":"Mol. Gen. Genet."},{"key":"2021110312483830700_B38","first-page":"569","article-title":"Activation in vivo of the minimal replication origin beta of plasmid R6K requires a small target sequence essential for DNA looping","volume":"4","author":"Kelley","year":"1992","journal-title":"New Biol."},{"key":"2021110312483830700_B39","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1093\/nar\/25.2.447","article-title":"Alanine-stretch scanning mutagenesis: a simple and efficient method to probe protein structure and function","volume":"25","author":"Lefevre","year":"1997","journal-title":"Nucleic. Acids. Res."},{"key":"2021110312483830700_B40","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/srep00509","article-title":"Nucleoprotein filament formation is the structural basis for bacterial protein H-NS gene silencing","volume":"2","author":"Lim","year":"2012","journal-title":"Sci. Rep."},{"key":"2021110312483830700_B41","doi-asserted-by":"crossref","first-page":"13134","DOI":"10.1093\/nar\/gku1051","article-title":"Timely binding of IHF and Fis to DARS2 regulates ATP-DnaA production and replication initiation","volume":"42","author":"Kasho","year":"2014","journal-title":"Nucleic Acids. Res."},{"key":"2021110312483830700_B42","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1073\/pnas.1212070110","article-title":"DnaA binding locus datA promotes DnaA-ATP hydrolysis to enable cell cycle-coordinated replication initiation","volume":"110","author":"Kasho","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021110312483830700_B43","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1093\/nar\/gkab113","article-title":"Defining a novel domain that provides an essential contribution to site-specific interaction of Rep protein with DNA","volume":"49","author":"Wegrzyn","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2021110312483830700_B44","doi-asserted-by":"crossref","first-page":"e58061","DOI":"10.7554\/eLife.58061","article-title":"Primary and promiscuous functions coexist during evolutionary innovation through whole protein domain acquisitions","volume":"9","author":"Escudero","year":"2020","journal-title":"Elife"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/49\/19\/11119\/41071270\/gkab903.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/49\/19\/11119\/41071270\/gkab903.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T08:51:55Z","timestamp":1635929515000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/49\/19\/11119\/6395345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,13]]},"references-count":44,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10,13]]},"published-print":{"date-parts":[[2021,11,8]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkab903","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.740979558.793589474","asserted-by":"object"}]},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,11,8]]},"published":{"date-parts":[[2021,10,13]]}}}