Rôle des complexes RecBC dans la protection de l’ADN en cours de synthèse lors d’un blocage réplicatif

In the team, we are interested to understand how a damaged DNA is replicated, using both bacteria and yeast as model organisms. Replication blockage due to an unrepaired lesion is a common event that drives genome instability by leading to mutations, double strand breaks or chromosomal rearrangements that can result in cancer in humans. Understanding how cells handle this blockage is thus necessary to preserve genome stability, yet we lack mechanistic insights at the level of a single lesion event. In the laboratory, we set up a unique genetic system able to insert a single replication blocking lesion into a living cell. Using this system, we have recently unraveled in Escherichia coli a novel structural role for the RecBC complex in protecting the 3′-end of the nascent DNA from nucleolytic degradation. We are now interested in identifying and characterize the factors involved in the mechanisms of protection/degradation of the nascent DNA. We will employ a genetic approach together with in vitro reconstitution experiments to determine those mechanisms.