Molecular mechanisms of genotoxic stress response

Group leader : Jean MOLINIER

Research area

Genotoxic stress exposure (i.e, UV) can affect cell integrity and can damage both nuclear (DNA) and cytoplasmic (RNAs)compartments impairing (epi)genome integrity and gene expression (transcription and translation). Thus, the capacity of living organisms to cope with the damaging effect of genotoxic agents relies on interplays between different surveillance processes preventing deleterious chromosome rearrangements, epigenome alterations and collapse of transcriptional/translational machinery. We are interested in deciphering the underlying molecular mechanismscontrolling (epi)genome integrity and translation in response to genotoxic stress exposure.


(Epi)genome surveillance

The formation of DNA damages and the choice of the repair pathway depend on the chemical environment of the DNA molecule. The crosstalk between DNA repair and chromatin shape might participate in modulating the environment of the DNA to avoid further damage accumulation or to act as epigenetic memory to prevent undesired genome rearrangements. Therefore, it is of prime interest to better understand the mechanisms related to DNA damage formation, recognition and repair in the context of chromatin complexity. We aim at deciphering the reciprocal crosstalk between epigenetics, UV-induced DNA damages and DNA repair processes using genetic, genomic approaches and mutant plants.

Translational surveillance

Protein synthesis often plays a pivotal role in controlling gene expression in eukaryotes, especially under stress conditions. Accumulation of damages in mRNA leads to the accumulation of collided ribosomes and thus translational arrest. TOR as master stress-related kinase adjusts ribosome turnover rates with the needs for translation efficiency and autophagy-dependent recycling. We aim at understanding how the TOR kinase functions at the molecular level and how changes in its activity lead to translational control upon genotoxic stress exposure. We expect to provide a high-resolution picture of gene expression changes during genotoxic stress response affecting translational reprogramming. In addition, we will characterize the role of PI3KK family members (ATM, ATR and TOR) in translational control of genotoxic stress response.