Conflicts between DNA replication fork progression and transcriptional regulation

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All organisms must duplicate their genetic material so that it can be passed from one generation to the next. However, this process occurs in a crowded environment since other equally important cellular functions must occur at the same time as DNA replication. As a result, genome duplication must occur even though the DNA is coated with many DNA binding proteins. Little is known of the effects of these DNA binding proteins upon replication even though there is much indirect evidence that such collisions lead to mutations in the DNA. We aim to use the replication machinery from a bacterium to analyse the effects of proteins bound to the DNA upon replication. We will measure the probability of DNA binding proteins halting the replication machinery, and will characterise the properties of protein-DNA complexes which lead to blockage of replication. However, cells clearly do have the ability to replicate their genomes even though the DNA is coated in a panoply of proteins. We will therefore search for enzymes that can help the replication machinery to move through DNA-protein complexes. These experiments will help us understand how all cells duplicate their genomes in a complex protein-rich environment. They may also cast light on how cells minimise the chances of their replication machinery stalling and causing potentially harmful mutations.