High performance motoring - replication fork movement in a complex environment

DNA复制是遗传蓝图代代相传的关键。此外，DNA的复制必须尽可能精确。即使在复制过程中出现的小错误也可能导致人类遗传疾病和癌症的发展。为了尽量减少在DNA复制过程中出现这种错误的可能性，所有生物都进化出了复杂的生物机器，以快速而准确地完成这一过程。然而，最近的研究表明，尽管进化做出了最大的努力，但这种DNA复制机制确实会崩溃。如果不重新启动，这些故障将导致基因蓝图中出现潜在的灾难性错误。我们已经开发出一种系统，利用细菌的简单DNA复制装置来监测复制的中断。目前的提案旨在确定复制机器的特征，以帮助最大限度地减少其故障。但是当复制中断时，有些系统会尝试重新启动复制过程。因此，我们也将尝试确定修复系统是否与复制机制相互作用，以帮助使修复过程更有效。因此，这些研究的目的是描述生物体如何尽量减少DNA复制出错的机会，以试图避免遗传物质中产生缺陷的灾难性后果。

DNA replication is essential to pass on the genetic blueprint from one generation to the next. Moreover, duplication of DNA must be done with the highest possible accuracy. Even small mistakes arising during the duplication process can lead to the development of genetic disease and cancers in humans. To minimise the possibility of such mistakes being made during DNA replication, all organisms have evolved complex biological machines to perform this process both speedily and accurately. However, recent work has shown that despite the best efforts of evolution, this DNA replication machinery does break down. If not restarted, these breakdowns lead to potentially catastrophic errors arising in the genetic blueprint. We have developed a system to monitor the breakdown of replication using the simple DNA replication apparatus of a bacterium. This current proposal aims to determine the features of replication machines that help minimise their breakdown. But when replication does break down, there are systems that attempt to restart the replication process. We will therefore also try and establish whether the repair systems interact with the replication machinery to help make the repair process more efficient. These studies therefore aim to characterise how organisms minimise the chances of DNA duplication going awry to try and avoid the disastrous consequences of defects arising within the genetic material.