Determining the role and mechanism of action of the SUMO targeted ubiquitin ligase RNF4 in maintaining genome integrity

RNF4 is a protein that is important for maintaining the stability of the genome in higher eukaryotic cells. Professor Hay is aiming to define the role of RNF4 in the cellular response to DNA damage and to establish the molecular mechanism that is employed by RNF4 to catalyse the transfer of ubiquitin to substrates. Specifically, he will use quantitative proteomics to identify proteins that are targeted by RNF4 in response to genotoxic stress and he will establish how the RNF4-dependent ubiquitination leads to a functional change in protein activity. The impact of DNA-damaging cancer therapies is attenuated by the DNA repair process, so a better understanding of the actions of RNF4 may help in the design of DNA repair inhibitors that could have an enhanced effectiveness against cancer cells.