High performance motoring - replication fork movement in a complex environment

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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.