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Adresse : Université Catholique de Louvain (UCL). Institut des Sciences de la Vie (ISV), Place Croix du Sud, 4/5 L7 07 06, B-1348 Louvain-la-Neuve, Belgique

Composition :
Bernard HALLET (PR Louvain)
Gérôme Goossens (teaching and research assistant)
Nathan Nguyen (Tech)

Activité scientifique : Tn4430 is a member of the widespread Tn3-family of transposons that are especially notorious for the dissemination of antibiotic resistance genes amongst bacteria. Transposition of Tn4430 is a two-step process requiring the consecutive action of two transposon-encoded proteins; the DDE-transposase TnpA and the Y-recombinase TnpI. In the first step of the reaction, TnpA co-operate with the host replication machinery to generate an intermediate termed ‘cointegrate’ carrying duplicated copies of the transposon. The TnpI recombinase acts during the second step of the process to resolve de cointegrate by catalysing a reciprocal site-specific recombination reaction between both copies of the element.
Our work on the TnpI recombinase has unveiled a unique mechanism to control the selectivity and directionality of the recombination reaction through the assembly of a topologicaly defined higher-order nucleoprotein complex comprising regulatory TnpI bound to accessory DNA sequences of the recombination sites and catalytic TnpI subunits bound on the recombination core sites.
More recent progress made in the functional characterization of the TnpA protein based on both in vivo and in vitro assays showed that Tn4430 transposition is controlled at an early step of transposition complex assembly, possibly requiring a proper target for triggering catalysis.  Further work on Tn443O targeting mechanism led us to propose a new model for replicative transposition, referred to as the ‘replisome hijacking model’, according to which replicative transposons insert into ongoing replication forks as a mechanism to recruit the host replication machinery during transposition. This mechanism challenges current models for replicative transposition as they generally found in textbooks.


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