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动态平衡所需的所有信息。每天，我们基因组的完整性都受到DNA双链断裂的威胁。如果这些损伤修复不当，我们的基因组就会积累变化，这些变化可能会破坏细胞的基本功能，最终导致细胞死亡。幸运的是，我们基因组的完整性得到了一个复杂的蛋白质网络的保障，细胞已经进化出这个网络来检测、发送信号并有效地修复受损的DNA。在细胞中，我们的基因组由一种名为“染色质”的结构中的蛋白质组成。在DNA损伤时，断裂周围的染色质被标记上一个标记，这是随后招募双链断裂信号和修复蛋白所必需的。最近，我们发现了一些信号和修复蛋白与这个标记特异结合的机制。染色质是一种动态结构，在不同的细胞环境中会有所不同。因此，我们将研究不同染色质状态如何影响结合到断裂周围标记染色质的蛋白质的招募。为了实现这一目标，我们将使用一系列生化和生物学方法来绘制染色质的修饰图，这些染色质调控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. **