Louvain Institute of Biomolecular Science and Technology – Team Hallet
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Louvain Institute of Biomolecular Science and Technology (LIBST), Université Catholique de Louvain (UCL)
Place Croix du Sud, 4/5 L7.07.06
B-1348, Louvain-La-Neuve
Belgium
Scientific Interest
Transposon Tn4430 belongs to a widespread family of bacterial transposons, the Tn3 family, that is notorious for its prevalence in the dissemination of antibiotic resistances among pathogens. In spite of this, the molecular mechanisms that control the mobility of these elements have long remained ill defined. We have recently achieved several breakthroughs in the understanding of these mechanisms, making of Tn4430 a new paradigm for the study of Tn3-family transposons. (I) For the first time, we were able to reconstitute critical steps of the transposition reaction in vitro, allowing to study the assembly of the transposition complex and its activation. (II) Together with complementary genetic evidence, this study has unveiled an unexpected interaction between the transposition mechanism and DNA replication. The data support a new “replisome hijacking” model of transposition along which Tn3-family transposons integrate into replication and/or DNA repair intermediates in order to recruit the host replication machinery during the transposition process. (III) Finally, we recently succeeded to build-up the first 3-D models for the transposition complex, based on high-resolution Cryo-EM (cryo-electron microscopy), opening the route for deciphering the transposition mechanism at the atomic level.
Transposon Tn4430 belongs to a widespread family of bacterial transposons, the Tn3 family, that is notorious for its prevalence in the dissemination of antibiotic resistances among pathogens. In spite of this, the molecular mechanisms that control the mobility of these elements have long remained ill defined. We have recently achieved several breakthroughs in the understanding of these mechanisms, making of Tn4430 a new paradigm for the study of Tn3-family transposons. (I) For the first time, we were able to reconstitute critical steps of the transposition reaction in vitro, allowing to study the assembly of the transposition complex and its activation. (II) Together with complementary genetic evidence, this study has unveiled an unexpected interaction between the transposition mechanism and DNA replication. The data support a new “replisome hijacking” model of transposition along which Tn3-family transposons integrate into replication and/or DNA repair intermediates in order to recruit the host replication machinery during the transposition process. (III) Finally, we recently succeeded to build-up the first 3-D models for the transposition complex, based on high-resolution Cryo-EM (cryo-electron microscopy), opening the route for deciphering the transposition mechanism at the atomic level.
Thematic