Macromolecular assemblies and mechanisms of DNA replication and repair.

Every time a human cell divides, it must copy three billion DNA letters without error while simultaneously repairing damage from sunlight, chemicals, and normal cellular activity. This project aims to solve the atomic-level structures of the protein machines that perform these two essential tasks. One machine, the nucleoprotein filament, orchestrates DNA recombination—the process that swaps genetic material between chromosomes to repair dangerous breaks. The other, the pol α/primase complex, kickstarts DNA replication by synthesising the first few building blocks of a new DNA strand. Without these molecular assemblies working correctly, cells accumulate mutations that drive cancer and other genetic diseases. This is fundamental science. There is no immediate clinical application. But understanding exactly how these protein machines move and interact at the atomic scale provides the blueprint for future drug design. Many existing cancer chemotherapies already target DNA replication enzymes, but they are blunt instruments with severe side effects. Knowing the precise architecture of these assemblies could eventually allow researchers to design molecules that block only the faulty versions found in tumour cells, leaving healthy cells untouched.