Nucleotide Excision Repair - Lighting up a Dark Pathway

核苷酸切除修复——照亮黑暗之路

• 批准号: BB/R015570/1
• 负责人: Malcolm White
• 金额: $ 63.11万
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR015570%2F1
• 关键词: Nucleotide; Excision; Repair; Lighting; up

Nucleotide Excision Repair (NER), also known as "Dark Repair", is a DNA repair pathway essential for all forms of life including humans. Mutations in this pathway lead to devastating diseases such as xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) with elevated cancer levels and premature ageing. NER is highly complex, involves many different proteins, and is still not well understood. There are particular hurdles in the study of dynamic processes such as NER that involve transient interactions of large protein and DNA complexes. Advances in protein production and in new techniques to study molecules one at a time (thus avoiding averaging effects) have opened the door to new ways to study and understand these complex processes, and we now have all the tools we need to study NER in detail. By "lighting up" individual protein complexes we can follow their behavior in real time, and their interactions with other DNA and protein species. Recent advances in structural biology techniques will allow these large protein complexes to be studied at a molecular level. This work will advance technology and lead to a step change in our fundamental knowledge of a key aspect of our biology, essential for healthy ageing.

核苷酸切除修复（NER），也被称为“暗修复”，是包括人类在内的所有生命形式必不可少的DNA修复途径。这一途径的突变可导致破坏性疾病，如色素干皮病（XP）和毛硫营养不良（TTD），并伴有癌症水平升高和过早衰老。NER是高度复杂的，涉及许多不同的蛋白质，并且仍然没有被很好地理解。在动态过程的研究中有一些特殊的障碍，例如涉及大蛋白质和DNA复合物的瞬时相互作用的NER。蛋白质生产的进步和每次研究一个分子的新技术（从而避免平均效应）为研究和理解这些复杂过程的新方法打开了大门，我们现在拥有了详细研究NER所需的所有工具。通过“点亮”单个蛋白质复合物，我们可以实时跟踪它们的行为，以及它们与其他DNA和蛋白质物种的相互作用。结构生物学技术的最新进展将使这些大型蛋白质复合物能够在分子水平上进行研究。这项工作将推动技术的发展，并导致我们对生物学关键方面的基础知识的逐步改变，这对健康老龄化至关重要。

项目成果

Facile and scalable expression and purification of transcription factor IIH (TFIIH) core complex.

转录因子 IIH (TFIIH) 核心复合物的简便且可扩展的表达和纯化。

• DOI: 10.1016/j.pep.2020.105660
• 发表时间: 2020
• 期刊: Protein expression and purification
• 影响因子: 1.6
• 作者: Sanles-Falagan R