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

转录调节因子和 RNA 成熟因子在维持基因组稳定性中的作用

• 批准号: RGPIN-2016-05026
• 负责人: Maréchal, Alexandre
• 金额: $ 2.26万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=628943
• 关键词: Roles; Transcriptional; Regulators; RNA; Maturation

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.

我们经常面临压力，这些压力会损害我们的遗传物质并可能导致突变。突变会导致癌症等与年龄相关的疾病。幸运的是，我们的细胞配备有蛋白质，可以检测损伤并保护我们的基因组免遭降解。我们最近发现了许多识别基因组断裂区域的新蛋白质。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抵抗力尤其重要，从而帮助细胞修复DNA。为了弄清楚 PRP19 如何保护我们的基因组免受突变，我们将确定 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极其精确和新颖的观点：蛋白质如何保护我们的 DNA、为什么基因组中的某些位置比其他位置更频繁地断裂，以及如何稳定这些脆弱位点并防止突变。