Sixième réunion du GdR Architecture et Dynamique Nucléaire (ADN)

Imaging DNA repair at the single molecule level

Non programmé

15m

Orateur

Mlle judith Miné-Hattab (Institut Curie)

Description

Our genome is constantly damaged by a variety of exogenous and endogenous agents. Among the various forms of DNA damage, double-strand breaks (DSBs) are the most cytotoxic and genotoxic for the cell. Failure to repair such lesions leads to genomic instability or cell death. In higher eukaryotes, mutations in DNA repair genes lead to cancer predisposition. Eukaryotic organisms use several mechanisms to repair DSBs: non-homologous end-joining (NHEJ), alternative non-homologous end-joining (Alt-NHEJ) and homologous recombination (HR). Here, we investigate the molecular mechanisms of HR proteins inside cells at the single molecule level in living Saccharomyces cerevisiae yeast. In response to DSB, repair proteins colocalize from diffuse distribution to repair foci located at the damaged DNA site. An enduring question in the DNA damage field is how do repair proteins find their correct target and accumulate within repair foci: how do they diffuse before DNA damage, during focus formation when they have to reach the site of damage, and inside such a small sub-nuclear region formed by a repair focus? To answer these questions, we use single particle tracking and PALM approaches allowing us to assess the physical properties underlying repair foci formation and decipher the internal structure of these foci.