Aim
The aims of our research are to understand how DNA double-strand breaks (DSBs) are repaired in the context of chromatin and what dictates the repair pathway choice. DSBs are mainly repaired by either Non-Homologous End Joining (NHEJ) or Homologous Recombination (HR). When inaccurately used, these repair pathways have dramatically different consequences on the genome; for example, translocations mainly caused by Alt-NHEJ, or repeat amplifications provoked by the use of unequal HR. The choice between all the available pathways is thus a critical aspect of DSB repair. However, how this choice is executed is far from being understood.
To address the molecular mechanisms at play, we developed the DIvA cell line, which is a powerful experimental cell system that enables the creation of DSBs at well-known positions across the genome in various chromatin contexts and which has the advantage of detaining statistical power over a large range of DSBs.
Questions addressed
How does the chromatin state influence the recognition of DSB and the repair pathway choice?
How are active genes repaired?
How do chromosome conformation changes following DSB?
