Description du sujet de thèse

Elucidation of the molecular Interactions controlling Xer recombination
Bacteria have evolved a highly conserved tyrosine recombination machinery, Xer, to resolve chromosome dimers by adding a crossover at a specific site, dif. Xer also mediates the integration of many mobile elements into their host genome by recombining dif and a dif-like attachment site, attP, carried by the mobile element. Two features distinguish the Xer system from paradigmatic tyrosine recombination systems. First, tyrosine recombination systems are generally composed of a single tyrosine recombinase. In contrast, with the exception of a few species, Xer is composed of two tyrosine recombinases, XerC and XerD, which each bind to a specific arm of the recombination sites and catalyse the exchange a specific pair of strands . Thus, two recombination pathways can be considered, depending on whether XerC or XerD initiates the recombination reaction. Second, XerD is inactive by default. The integration of various phages exploiting Xer, including the Vibrio cholerae Cholera-ToXin phage (CTXΦ), is initiated by XerC. However, chromosome dimer resolution and the integration of the V. cholerae Toxin-Linked Crytic phage satellite (TLCΦ) both depend on the XerD-first pathway. Genetic and biochemical experiments have shed light on the protein factors that control the XerC and XerD-first pathways. The aim of the doctoral elucidate the molecular interactions that control Xer recombination by an integrative approach combining crystallography, cryoEM, in vitro biochemical assays and in vivo molecular genetics assays.

Contexte de travail

Work will be undertaken in the Evolution and Maintenance of Circular Chromosomes team in the genome biology department of the Institute of Integrative Cell Biology (I2BC). The Instirute is located in the CNRS campus of Gif sur Yvette.

Contraintes et risques

Depending on beamline and/or cryoEM availability some experiments might need to be undertaken at night of during the weekend.