Grant: Project Grant

Proteins undergo chemical modifications to function properly. However, when these modifications are aberrant, they can cause or underly human diseases. Despite significant efforts to identify the position of these modifications in proteins, assessing their relevance remains difficult. Here, we develop a functional genomics platform to elucidate the function of protein modifications in humans. We employ a very precise and accurate method to edit genes, known as prime editing, to reveal the connection between protein modifications and cellular functions. The scale of this approach is designed to interrogate a large number of modified residues in multiple contexts at a time. We will apply this platform for large-scale discovery and characterization of new ways to help to keep our DNA safe. Our study will focus on identifying functionally relevant Proliferating Cell Nuclear Antigen (PCNA) modifications involved in protecting cells against the impact of cancer drugs that damage DNA. Together, these studies will develop a novel genomics platform to accelerate the discovery of important protein modifications in human biology.