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: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=523310
• 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许多广泛传播的化学试剂会损害我们的遗传物质 (DNA)。 DNA 的损伤必须得到修复，否则细胞会以极快的速度积累基因改变，从而增加患癌症等疾病的风险。 然而，所有细胞都拥有许多不同类型的 DNA 修复蛋白，可以有效地将受损的 DNA 恢复为其天然形式。 其中一些蛋白质仅修复 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，患有着色性干皮病的患者无法修复阳光引起的 DNA 损伤。 因此，这些患者皮肤癌的发病率很高。 我们在一种名为秀丽隐杆线虫的小蠕虫中发现了两种 DNA 修复蛋白，这种生物体已被用作理解许多生物过程的简单模型系统。 我们正在通过了解这些 DNA 修复蛋白可以修复的 DNA 损伤类型来确定这些 DNA 修复蛋白在秀丽隐杆线虫中的生物学作用。我们将使用特殊技术来防止这些 DNA 修复蛋白纠正线虫中受损的 DNA。 在这种情况下，当暴露于环境 DNA 损伤剂时，特别是当其他 DNA 修复过程不存在时，蠕虫预计无法存活。 缺乏这些 DNA 修复蛋白的蠕虫可以用作敏感的报告系统来测量环境（土壤和水）中污染物的水平。