Deciphering the impact of chromatin modifications on DNA repair processes

基因组是一个DNA序列，它编码了在我们整个身体中建立和维持稳态所需的所有信息。每天，我们基因组的完整性都受到DNA双链断裂的威胁。如果这些损伤被不适当地修复，我们的基因组就会积累改变，这些改变会使细胞的基本功能失调，最终导致细胞死亡。幸运的是，我们基因组的完整性受到一个复杂的蛋白质网络的保护，细胞已经进化到检测，信号和有效修复受损的DNA。在细胞中，我们的基因组与蛋白质组装在一个名为“染色质”的结构中。在DNA损伤时，断裂周围的染色质被标记为随后募集双链断裂信号传导和修复蛋白所需的标记。最近，我们发现了这些信号和修复蛋白中的一些特异性结合到该标记的机制。染色质是一种动态结构，在不同的细胞环境中变化。因此，我们将研究如何招募蛋白质结合到周围的断裂标记的染色质，是由不同的染色质状态的影响。为了实现这一目标，我们将使用一系列的生物化学和生物学方法来绘制染色质的修饰，这些修饰调节DNA双链断裂的检测和修复。在全球范围内，这些研究将增加我们对染色质有助于维持细胞基因组完整性的机制的了解。

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.