Nucleotide Excision Repair - Lighting up a Dark Pathway
Nucleotide Excision Repair - Lighting up a Dark Pathway
批准号:
BB/R015570/1
负责人:
Malcolm White
金额:
$63.11万
依托单位:
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
项目状态:
已结题
起止时间:
2018 至 --
中文摘要
核苷酸切除修复(NER),也称为“暗修复”,是包括人类在内的所有生命形式所必需的DNA修复途径。该途径中的突变导致毁灭性疾病,如着色性干皮病(XP)和甲状腺营养不良(TTD),癌症水平升高和过早衰老。NER非常复杂,涉及许多不同的蛋白质,并且仍然没有得到很好的理解。在动态过程的研究中有特别的障碍,如NER,涉及大蛋白质和DNA复合物的瞬时相互作用。蛋白质生产的进步和一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,我们可以在真实的时间内跟踪它们的行为,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允许在分子水平上研究这些大的蛋白质复合物。这项工作将推动技术进步,并导致我们对生物学关键方面的基本知识发生重大变化,这对健康老龄化至关重要。
英文摘要
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.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
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]
通讯作者:
Sanles-Falagan R
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The CRISPR system: a new frontier in prokaryotic molecular biology
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财政年份:2009
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依托单位:
Mechanism interactions and function of the structure specific nuclease XPF
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财政年份:2006
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负责人:Malcolm White
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依托单位:
海外基金