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Accueil > Départements > Biologie des Génomes > François-Xavier BARRE : Evolution et Maintenance des Chromosomes Circulaires

François-Xavier BARRE : Présentation de l’équipe

The team explores the interplay between DNA synthesis, chromosome segregation and cell division in bacteria. We use Vibrio cholerae as a model organism because its genome is divided on two circular chromosomes, in contrast to most bacteria, and because it sits at a crossroad in the evolution.

Project overview

During cell proliferation, DNA synthesis, chromosome segregation and cell division must be coordinated to ensure the stable inheritance of the genetic material. In eukaryotes, this is achieved by checkpoint mechanisms that separate these processes in time. No such strict temporal separation exists in bacteria, in which DNA synthesis, chromosome segregation and cell division are concomitant. Instead, coordination is achieved by the interdependence of these processes.

The genome organization of bacteria is a key element in this coordination. Most bacteria harbor a single chromosome and, in the rare case in which the genetic material is divided on several chromosomes, the extra-numerous ones appear to have derived from horizontally acquired mega-plasmids that subsequently gained essential genes. This is notably the case for Vibrio cholerae, the agent of the deadly human diarrheal disease cholera, whose genome is divided between a 2.9 Mbp ancestral chromosome, chrI, and a 1 Mbp plasmid-derived chromosome, chrII. Bacterial chromosomes harbor a single origin of bidirectional replication and are generally circular. Replication ends in a region opposite of the origin of replication, the terminus region, in which is usually found a specific recombination site dedicated to the resolution of chromosome dimers, dif. Segregation is concurrent with replication. It starts with the active positioning of sister copies of the origin region into opposite cell halves. As replication progresses along the left and right chromosomal arms, newly replicated loci are progressively segregated towards their future daughter cell positions. In most cases, however, the replication terminus region of the chromosome remains at mid-cell at the time of cell division, which participates in the selection of the division site, the licensing of the division machinery assembly and the correct alignment of dif sites. The team explores the interplay between DNA synthesis, chromosome segregation and cell division in bacteria. The originality of the team’s approach comes from using (1) V. cholerae, a multi-chromosomal species, as a model organism and (2) the activity of the chromosome dimer resolution machinery as a tool analyse the management of bacterial chromosomes at the time of cell division.

V. cholerae choreography of chromosome segregation.
Blue : chrI origin region ; Green : chr1 mid-replichore ; Red : ChrI Ter region.

In V. cholerae, as in most bacteria, chromosome dimers are resolved by the addition of a crossover at dif by two tyrosine recombinases, XerC and XerD. From a structural and biochemical point of view, they belong to the Cre resolvase family. Correspondingly, they are exploited for the resolution of multimers of numerous plasmids. They are also exploited by mobile DNA elements to integrate into their host genome. CTXɸ, a filamentous bacteriophage that harbors the genes encoding cholera toxin - the principal virulence factor of epidemic V. cholerae strains, was the first identified Integrative Mobile Element exploiting Xer (IMEX). Cooperative interactions between CTXɸ and at least 2 other types of IMEX contribute to the rapid and continuous emergence of new cholera epidemic strains. In parallel to our bacterial cell cycle studies, we explore how the V. cholerae IMEXs convert dedicated tyrosine resolvases into integrases.

In vivo IMEX integration assay

Key Words

chromosome segregation, cell division, replication, tyrosine recombinase, cholera

Contact


BARRE Francois-Xavier [Directeur de Recherche - CNRS]
Equipe Barre FX. - Evolution et maintenance des Chromosomes circulaires [Responsable]
01 69 82 32 24 Gif - Bât 26

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