Sosnovsky Lectureship Series – Guest Speaker Prof. Marc Greenberg from Johns Hopkins University

Chemical Tools for DNA-Protein Cross-Link Formation and Study

DNA-protein cross-links (DPCs) are highly toxic lesions formed via a variety of chemical pathways and as intermediates in enzyme transformations. DPCs are potent blocks of helicases, as well as DNA and RNA polymerases. DPCs are associated with aging and diseases such as cancer. Recently, DPCs were also shown to result in chronic inflammation. Despite their importance, our understanding of DPCs has lagged that of other forms of DNA damage. For instance, the first protease identified to repair DPCs in human cells (SPRTN) was only identified in the past decade. Our group is developing chemical tools for producing DPCs. These tools are useful for studying DPCs extra- and intracellularly and are potentially useful pharmacologically. Recent published and unpublished investigations will be presented.