Roles of Transcriptional Regulators and RNA Maturation Factors in the Maintenance of Genomic Stability

我们不断地暴露在压力下，这些压力会破坏我们的遗传物质，并可能导致突变。突变导致与年龄相关的疾病，如癌症。幸运的是，我们的细胞配备了蛋白质，可以检测损伤并保护我们的基因组免受降解。我们最近发现了许多能够识别基因组断裂区域的新型蛋白质。这些蛋白质如何保护基因组目前尚不清楚。在这些因素中，我们发现PRP19对于化疗药物和辐射的抗性特别重要，从而帮助细胞修复其DNA。为了弄清楚PRP19如何保护我们的基因组免受突变的影响，我们将确定我们DNA中受PRP19保护的特定区域。我们将研究这些区域的特征，以及当PRP19从细胞中去除时它们会发生什么。这将为我们带来一个非常精确和新颖的观点，即蛋白质如何保护我们的DNA，为什么基因组中的某些地方比其他地方更频繁地断裂，以及可以做些什么来稳定这些脆弱的位点并防止突变。

We are constantly exposed to stresses that damage our genetic material and may cause mutations. Mutations lead to age-related diseases such as cancer. Fortunately, our cells are equipped with proteins that can detect damage and protect our genome from degradation. We have recently identified many novel proteins that recognize broken regions of the genome. What these proteins do to protect the genome is currently unknown. Among these factors, we found that PRP19 is particularly important for the resistance to chemotherapeutic drugs and irradiation and thus helps cells repair their DNA. To figure out how PRP19 shields our genome against mutations, we will identify the specific regions of our DNA that are protected by PRP19. We will study the characteristics of these regions and what happens to them when PRP19 is removed from cells. This will bring us an extremely precise and novel point of view on how proteins safeguard our DNA, why some places in the genome break more frequently than others and what could be done to stabilize these fragiles sites and prevent mutations.