Elucidating the molecular basis for DNA primer synthesis

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Our cells and those from all living organisms contain DNA, the so called "genetic blueprint of life", that encodes the information for all our genes. DNA has a simple repeating polymeric structure composed of two complementary strands of DNA composed of bases, which form long, string-like, double-helical structures that make up the genome. Our genome is packaged away into chromosomes, contained within the nucleus of nearly every cell. This information must be faithfully copied as cells divide to produce daughter cells. Cells produce a large number of proteins responsible for "photocopying" this DNA blueprint. The proteins tasked with accurately copying the cell's genetic code are called DNA polymerases. However, polymerases are unable to produce or copy DNA from scratch and require the synthesis of a short primer from which to copy the bulk of the genomic DNA. Fortunately, all cells possess a priming enzyme called DNA primases, whose role it is to make these initiating primers, although how they produce these short polymers from is still poorly understood. In this research programme, we are proposing to determine how DNA primases, from bacteria and human cells, are able to perform the essential task of primer synthesis. This proposal will provide critical insights into this fundamental replicative mechanism that is essentially required for DNA synthesis in all cells. Understanding priming mechanisms that initiate and maintain efficient DNA replication will help uncover new strategies to treat conditions and diseases associated with uncontrolled proliferation, such as cancer and microbial infections.