Genome duplication is essential for the propagation of cellular organisms, yet errors that occur during DNA replication are a source of genomic instability and a central factor contributing to cancer. Normally, replication-coupled DNA repair mechanisms protect cells from genomic instability, but often these essential systems go wrong in cancer. The long-term research goal of the lab is to elucidate the mechanisms governing replication-coupled DNA repair in normal and cancer cells. This will provide a deeper understanding of these processes and ultimately inform novel therapeutic anticancer strategies.
The complex protein interplay within DNA repair pathways requires fine spatiotemporal regulation which is achieved, in part, by post-translational modifications (PTMs) such ADP-ribosylation, phosphorylation and ubiquitylation. PTM signalling provides a multifaceted mechanism to control various aspects of protein function, including localisation, turnover and activation or repression. Importantly, enzymes involved in the regulation of PTM signalling are attractive anticancer targets. Our research aims to understand the roles and mechanisms of PTM signalling within the context of replication-coupled DNA repair.
To address our research aims, we use a range of biochemical, cellular and genetic (e.g. CRISPR-Cas9) approaches, which are supported by the world-class facilities in the Department of Biochemistry and broader Oxford research environment.