Mechanism of a nucleotide dependent transcription activation process

核苷酸依赖性转录激活过程的机制

基本信息

批准号：
BB/H011234/1
负责人：
Peter Stockley
金额：
$ 57.69万
依托单位：
University of Leeds
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2010
资助国家：
英国
起止时间：
2010 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FH011234%2F1
关键词：
Mechanism nucleotide dependent transcription activation

项目摘要

The cells of every organism contain a chemical code within their DNA molecules that holds the information needed for making all the protein products required to make the cell grow and stay alive. The code is in the form of a linear sequence of nucleotide bases, the famous A,G, C & T. The order of these letters determines the subsequent linear order of amino acids of the cell's proteins, which ultimately determine its structure and function. Converting the nucleotide information into the encoded amino acid sequence is known as as gene expression. The first step in this process is one of the most important reactions inside cells and involves making an RNA copy - a transcript- of the DNA message. The enzymes involved in this process - RNA polymerases - must start the copying process at a defined point in DNA, known as the promoter. In cells, this process is tightly regulated and determines the pattern of genes being read and thus contributes to the precise execution of the cellular genetic program. We are studying the basic mechanisms that control the choice of start site and the controlled activation of the RNA polymerase from a passive DNA-binding protein into the active copying machine. In particular we are studying how the protein components of transcription machinery use the energy currency of the cell-a molecule called ATP-to function as small machines and to interconvert between different states. We would like to know the detailed features and the conformational changes in the transcription machinery during the initial steps - when the double stranded DNA is opened up in single strand forms and the template strand is delivered into the site of RNAP for synthesizing RNA.

每个生物体的细胞的 DNA 分子中都含有化学密码，其中包含制造细胞生长和保持活力所需的所有蛋白质产物所需的信息。密码采用核苷酸碱基线性序列的形式，即著名的A、G、C和T。这些字母的顺序决定了细胞蛋白质随后的氨基酸线性顺序，从而最终决定其结构和功能。将核苷酸信息转化为编码的氨基酸序列称为基因表达。该过程的第一步是细胞内最重要的反应之一，涉及制作 DNA 信息的 RNA 副本（转录本）。参与这一过程的酶——RNA 聚合酶——必须在 DNA 中的一个定义点（称为启动子）开始复制过程。在细胞中，这个过程受到严格调节，决定了基因读取的模式，从而有助于细胞遗传程序的精确执行。我们正在研究控制起始位点选择和 RNA 聚合酶从被动 DNA 结合蛋白到主动复制机的受控激活的基本机制。特别是，我们正在研究转录机器的蛋白质成分如何使用细胞的能量货币（一种称为 ATP 的分子）作为小型机器发挥作用并在不同状态之间相互转换。我们想知道转录机制在初始步骤中的详细特征和构象变化——当双链DNA以单链形式打开并且模板链被递送到RNAP位点以合成RNA时。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Domain movements of the enhancer-dependent sigma factor drive DNA delivery into the RNA polymerase active site: insights from single molecule studies.

DOI：
10.1093/nar/gku146
发表时间：
2014-04
期刊：
Nucleic acids research
影响因子：
14.9
作者：
Sharma A;Leach RN;Gell C;Zhang N;Burrows PC;Shepherd DA;Wigneshweraraj S;Smith DA;Zhang X;Buck M;Stockley PG;Tuma R
通讯作者：
Tuma R