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dc.contributor.authorAzzi-Martin, Lamia
dc.contributor.authorHe, Wencan
dc.contributor.authorPere-Vedrenne, Christelle
dc.contributor.authorKorolik, Victoria
dc.contributor.authorAlix, Chloe
dc.contributor.authorProchazkova-Carlotti, Martina
dc.contributor.authorMorel, Jean-Luc
dc.contributor.authorLe Roux-Goglin, Emilie
dc.contributor.authorLehours, Philippe
dc.contributor.authorDjavaheri-Mergny, Mojgan
dc.contributor.authorGrosset, Christophe F
dc.contributor.authorVaron, Christine
dc.contributor.authorDubus, Pierre
dc.contributor.authorMenard, Armelle
dc.date.accessioned2019-11-06T06:19:21Z
dc.date.available2019-11-06T06:19:21Z
dc.date.issued2019
dc.identifier.issn1553-7366
dc.identifier.doi10.1371/journal.ppat.1007921
dc.identifier.urihttp://hdl.handle.net/10072/388943
dc.description.abstractHumans are frequently exposed to bacterial genotoxins involved in digestive cancers, colibactin and Cytolethal Distending Toxin (CDT), the latter being secreted by many pathogenic bacteria. Our aim was to evaluate the effects induced by these genotoxins on nuclear remodeling in the context of cell survival. Helicobacter infected mice, coculture experiments with CDT- and colibactin-secreting bacteria and hepatic, intestinal and gastric cells, and xenograft mouse-derived models were used to assess the nuclear remodeling in vitro and in vivo. Our results showed that CDT and colibactin induced-nuclear remodeling can be associated with the formation of deep cytoplasmic invaginations in the nucleus of giant cells. These structures, observed both in vivo and in vitro, correspond to nucleoplasmic reticulum (NR). The core of the NR was found to concentrate ribosomes, proteins involved in mRNA translation, polyadenylated RNA and the main components of the complex mCRD involved in mRNA turnover. These structures are active sites of mRNA translation, correlated with a high degree of ploidy, and involve MAPK and calcium signaling. Additional data show that insulation and concentration of these adaptive ribonucleoprotein particles within the nucleus are dynamic, transient and protect the cell until the genotoxic stress is relieved. Bacterial genotoxins-induced NR would be a privileged gateway for selected mRNA to be preferably transported therein for local translation. These findings offer new insights into the context of NR formation, a common feature of many cancers, which not only appears in response to therapies-induced DNA damage but also earlier in response to genotoxic bacteria.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofpagefrome1007921:1
dc.relation.ispartofpagetoe1007921:27
dc.relation.ispartofissue9
dc.relation.ispartofjournalPLOS Pathogens
dc.relation.ispartofvolume15
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchcode1108
dc.subject.fieldofresearchcode0605
dc.subject.fieldofresearchcode1107
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsParasitology
dc.subject.keywordsVirology
dc.titleCytolethal distending toxin induces the formation of transient messenger-rich ribonucleoprotein nuclear invaginations in surviving cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationAzzi-Martin, L; He, W; Pere-Vedrenne, C; Korolik, V; Alix, C; Prochazkova-Carlotti, M; Morel, J-L; Le Roux-Goglin, E; Lehours, P; Djavaheri-Mergny, M; Grosset, CF; Varon, C; Dubus, P; Menard, A, Cytolethal distending toxin induces the formation of transient messenger-rich ribonucleoprotein nuclear invaginations in surviving cells, PLOS Pathogens, 2019, 15 (9), pp. e1007921:1-e1007921:27
dcterms.dateAccepted2019-06-18
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2019-10-31T05:00:24Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2019 Azzi-Martin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorKorolik, Victoria


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