Deciphering the impact of chromatin modifications on DNA repair processes

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The genome is a DNA sequence that encodes all the information required to build and sustain homeostasis in our entire body. Every day, the integrity of our genome is threatened by the introduction of DNA double-strand breaks. If these lesions are improperly repaired, our genome accumulates alterations that can deregulate essential functions of the cell and, ultimately, lead to cell death. Fortunately, the integrity of our genome is safeguard by a complex network of proteins that the cells have evolved to detect, signal and efficiently repair damaged DNA. In cells, our genome is assembled with proteins in a structure named “chromatin”. Upon DNA damage, the chromatin surrounding the breaks is labelled with a mark that is required for the subsequent recruitment of double-strand break signaling and repair proteins. Recently, we discovered the mechanisms by which some of these signaling and repair proteins bind specifically to this mark. Chromatin is a dynamic structure, which varies among different cellular contexts. Thus, we will investigate how the recruitment of proteins that bind to the marked chromatin around the break, is impacted by different chromatin states. To achieve this goal, we will use a series of biochemical and biological approaches to map the modifications of the chromatin that regulate the detection and repair of DNA double-strand breaks. Globally, these researches will increase our knowledge of the mechanisms by which chromatin contributes to the maintenance of genomic integrity in our cells.