The TRAIP ubiquitin ligase is a key regulator of genome integrity in mammalian cells. The importance of TRAIP is highlighted by the fact that mutation leads to a human disease syndrome, whilst over-expression of TRAIP can be associated with human cancer. Recent work has indicated that TRAIP associates with the replisome and ubiquitylates potential barriers in front of DNA replication forks, to activate DNA repair pathways. In addition, TRAIP is regulated during mitosis to destroy any remaining replisomes and allow for rapid processing of replication forks to facilitate chromosome segregation. It is likely that TRAIP has additional important targets that remain to be identified. This project will use a combination of cutting edge biochemical and molecular genetic techniques to identify and characterise novel targets of TRAIP, to explore their role in preserving genome integrity in mammalian cells. As well as being an exciting project in a fascinating area of fundamental cell biology, such new targets of TRAIP are also likely to be important in the context of human disease.