Investigating the physiological DNA replication initiation reaction

Genome duplication is required for cell proliferation in all organisms. This essential process involves the concerted activity of several multiprotein complexes to replicate an exact copy of the DNA. The bacterial DNA replication machinery is significantly simpler than the related eukaryotic system, making it well suited for detailed analysis. Additionally, the bacterial DNA replication machinery is an attractive drug target, and new antibiotics are urgently needed to combat drug-resistant strains. In all cells, chromosome replication requires key initiator proteins to unwind the DNA at specific sites called origins. Despite the fundamental importance of DNA replication initiation, crucial aspects of the process remain poorly understood.

I have developed new tools that allow the normally essential DNA replication initiation factors to be either removed or mutated. This opens the possibility of determining all of the sites in both the chromosome origin and the proteins required for the initiation of DNA replication.

My long-term goal is to expand this toolkit and investigate the entire DNA replication machinery.