Elucidating the molecular basis for DNA primer synthesis

阐明 DNA 引物合成的分子基础

基本信息

批准号：
BB/W015226/1
负责人：
Aidan Doherty
金额：
$ 101.82万
依托单位：
University of Sussex
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FW015226%2F1
关键词：
Elucidating molecular basis DNA primer

项目摘要

Our cells and those from all living organisms contain DNA, the so called "genetic blueprint of life", that encodes the information for all our genes. DNA has a simple repeating polymeric structure composed of two complementary strands of DNA composed of bases, which form long, string-like, double-helical structures that make up the genome. Our genome is packaged away into chromosomes, contained within the nucleus of nearly every cell. This information must be faithfully copied as cells divide to produce daughter cells. Cells produce a large number of proteins responsible for "photocopying" this DNA blueprint. The proteins tasked with accurately copying the cell's genetic code are called DNA polymerases. However, polymerases are unable to produce or copy DNA from scratch and require the synthesis of a short primer from which to copy the bulk of the genomic DNA. Fortunately, all cells possess a priming enzyme called DNA primases, whose role it is to make these initiating primers, although how they produce these short polymers from is still poorly understood. In this research programme, we are proposing to determine how DNA primases, from bacteria and human cells, are able to perform the essential task of primer synthesis. This proposal will provide critical insights into this fundamental replicative mechanism that is essentially required for DNA synthesis in all cells. Understanding priming mechanisms that initiate and maintain efficient DNA replication will help uncover new strategies to treat conditions and diseases associated with uncontrolled proliferation, such as cancer and microbial infections.

我们的细胞和来自所有生物体的细胞都包含DNA，即所谓的“生命的遗传蓝图”，它编码了我们所有基因的信息。 DNA具有一个简单的重复聚合物结构，由两个由碱基组成的DNA的互补链组成，它们形成了构成基因组的长，弦状的双螺旋结构。我们的基因组被包装成几乎每个细胞核中的染色体。该信息必须忠实地复制为细胞分裂以产生子细胞。细胞产生大量蛋白质，负责“影印”此DNA蓝图。精确复制细胞遗传代码的蛋白质称为DNA聚合酶。但是，聚合酶无法从头开始产生或复制DNA，并且需要合成短底漆，以从中复制大部分基因组DNA。幸运的是，所有细胞都有一种称为DNA起初的启动酶，尽管它们如何从中产生这些短聚合物的作用是使这些启动底漆的作用，但仍知之甚少。在该研究计划中，我们提议确定来自细菌和人类细胞中的DNA起点如何能够执行底漆合成的基本任务。该提案将为所有细胞中DNA合成所需的基本复制机制提供关键的见解。了解启动和维持有效的DNA复制的启动机制将有助于发现与不受控制的增殖相关的疾病和疾病的新策略，例如癌症和微生物感染。