Mechanism of a nucleotide dependent transcription activation process

核苷酸依赖性转录激活过程的机制

• 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

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.

每个生物的细胞都包含其DNA分子中的化学代码，该化学代码符合使所有蛋白质产物使细胞生长并保持生命所需的所有蛋白质产物所需的信息。该代码的形式是核苷酸碱基的线性序列，即著名的A，G，C＆T。这些字母的顺序确定了细胞蛋白的随后的氨基酸线性顺序，最终决定了其结构和功能。将核苷酸信息转化为编码的氨基酸序列被称为基因表达。此过程的第一步是细胞内部最重要的反应之一，涉及制作RNA副本 - DNA消息的转录本。参与此过程的酶 - RNA聚合酶 - 必须在DNA（称为启动子）的定义点开始复制过程。在细胞中，该过程受到严格的调节，并确定正在读取的基因模式，从而有助于精确执行细胞遗传程序。我们正在研究控制起始位点选择的基本机制，以及从被动DNA结合蛋白中的RNA聚合酶的受控激活，转化为活性复制机。特别是我们正在研究转录机械的蛋白质成分如何使用称为ATP-TO功能作为小型机器的细胞A分子的能量货币并在不同状态之间互连。我们想知道在初始步骤中转录机械的详细特征和构象变化 - 当双链DNA以单链形式打开时，将模板链传递到RNAP的位点中以进行合成RNA。

项目成果

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