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Dynamics of eukaryotic junction-resolving enzyme GEN1 - DNA junction interactions

真核连接解析酶 GEN1 与 DNA 连接相互作用的动力学

基本信息

批准号：
BB/P001491/1
负责人：
David Lilley
金额：
$ 43.85万
依托单位：
University of Dundee
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FP001491%2F1
关键词：
Dynamics eukaryotic junction resolving enzyme

项目摘要

Repair of damage to cellular DNA is extremely important to human health, and one important repair process is recombination. This involves the formation of branched structures in cellular DNA, that are then processed by enzymes. One such enzyme is called GEN1. We have recently solved the atomic structure of the GEN1 protein, and this structure has provided considerable insight into the probable mechanism of action. We now shall extend our knowledge by observation of single molecules of the enzyme as they carry out the processing of junctions, using highly sensitive fluorescence methods. We will be able to dissect the processes by which the protein binds to the DNA and assembles on the branched junction, and how it alters the structure of the DNA. We can then proceed to study the process by which the enzyme cuts the DNA of the junction at specific points, and how this is coupled to changes in structure. Our goal is a full understanding of how this enzyme achieves a well regulated processing of the junction. Our ultimate goal is to intervene in the process using small molecules, which could ultimately result in therapeutic agents.

细胞DNA损伤的修复对人类健康极为重要，其中一个重要的修复过程是重组。这涉及在细胞DNA中形成分支结构，然后由酶处理。这种酶被称为GEN1。我们最近已经解决了GEN1蛋白的原子结构，这个结构为可能的作用机制提供了相当多的见解。现在，我们将通过使用高灵敏度的荧光方法观察酶的单个分子进行连接的加工来扩展我们的知识。我们将能够剖析蛋白质与DNA结合并在分支连接处组装的过程，以及它如何改变DNA的结构。然后，我们可以继续研究酶在特定点切割连接处的DNA的过程，以及这如何与结构变化相结合。我们的目标是充分了解这种酶如何实现良好调节的连接处理。我们的最终目标是使用小分子干预这一过程，这最终可能导致治疗剂。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The role of RNA structure in translational regulation by L7Ae protein in archaea.

DOI：
10.1261/rna.068510.118
发表时间：
2019-01
期刊：
RNA (New York, N.Y.)
影响因子：
0
作者：
Huang L;Ashraf S;Lilley DMJ
通讯作者：
Lilley DMJ

A critical base pair in k-turns determines the conformational class adopted, and correlates with biological function.

DOI：
10.1093/nar/gkw201
发表时间：
2016-06-20
期刊：
Nucleic acids research
影响因子：
14.9
作者：
Huang L;Wang J;Lilley DM
通讯作者：
Lilley DM

Sequence determinants of the folding properties of box C/D kink-turns in RNA.

DOI：
10.1261/rna.063453.117
发表时间：
2017-12
期刊：
RNA (New York, N.Y.)
影响因子：
0
作者：
Ashraf S;Huang L;Lilley DMJ
通讯作者：
Lilley DMJ

Analysis of the Intrinsically Disordered N-Terminus of the DNA Junction-Resolving Enzyme T7 Endonuclease I: Identification of Structure Formed upon DNA Binding.

DOI：
10.1021/acs.biochem.6b00242
发表时间：
2016-08-02
期刊：
Biochemistry
影响因子：
2.9
作者：
Freeman AD;Stevens M;Declais AC;Leahy A;Mackay K;El Mkami H;Lilley DM;Norman DG
通讯作者：
Norman DG

Structure and ligand binding of the SAM-V riboswitch.