Biological function of the DNA repair enzyme APN-1 in C. elegans

线虫 DNA 修复酶 APN-1 的生物学功能

• 批准号: 202432-2012
• 负责人: Ramotar, Dindial
• 金额: $ 3.5万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=514063
• 关键词: Biological; function; DNA; repair; enzyme

Normal daily metabolism and many wide spread chemical agents in the environment can damage our genetic material (DNA). Damages to the DNA must be repaired otherwise cells would accumulate genetic alterations at an enormous rate escalating the risk of developing diseases such as cancers. However, all cells possess many different types of DNA repair proteins that efficiently restore the damaged DNA to its native form. Some of these proteins repair only specific damages to DNA. In several unfortunate cases, there are individuals that have deficiency in specific type of DNA repair proteins, for example, patients suffering from the disease Xeroderma pigmentosum cannot repair sunlight-induced DNA damages. As a result, these patients have a high incidence of skin cancer. We have identified two DNA repair proteins in a small worm called Caenorhabditis elegans, an organism that has been used as a simple model system to understand many biological processes. We are in the process of determining the biological role of these DNA repair proteins in C. elegans, by understanding the types of DNA lesions they can repair. We will use special techniques to prevent these DNA repair proteins from correcting damaged DNA in C. elegans. Under this condition, the worm is not expected to survive when expose to environmental DNA damaging agents and especially when other DNA repair processes are absent. Worms lacking these DNA repair proteins may be used as a sensitive reporter system to measure the level of contaminants in the environment (soil and water).

正常的日常新陈代谢和环境中广泛存在的化学物质会破坏我们的遗传物质（DNA）。对DNA的损害必须修复，否则细胞会以极快的速度积累遗传变异，从而增加患癌症等疾病的风险。然而，所有的细胞都拥有许多不同类型的DNA修复蛋白，这些蛋白可以有效地将受损的DNA恢复到其原始形式。其中一些蛋白质只修复DNA的特定损伤。在一些不幸的情况下，有些人缺乏特定类型的DNA修复蛋白，例如，患有色素性干皮病的患者无法修复阳光引起的DNA损伤。因此，这些患者的皮肤癌发病率很高。我们已经在一种叫做秀丽隐杆线虫的小蠕虫中发现了两种DNA修复蛋白，这种生物已经被用作理解许多生物过程的简单模型系统。通过了解这些DNA修复蛋白可以修复的DNA损伤类型，我们正在确定这些DNA修复蛋白在秀丽隐杆线虫中的生物学作用。我们将使用特殊的技术来防止这些DNA修复蛋白在秀丽隐杆线虫中纠正受损的DNA。在这种情况下，当暴露于环境DNA损伤剂，特别是当其他DNA修复过程不存在时，蠕虫预计不会存活。缺乏这些DNA修复蛋白的蠕虫可以作为一个敏感的报告系统来测量环境（土壤和水）中的污染物水平。