This project utilizes new methodologies and genetic tools to answer key open questions on the detection and repair of covalent DNA-protein crosslinks (DPCs). The repair of DPCs involves the proteolytic destruction of the protein adduct by the DPC-specific protease SPRTN or by proteasomal degradation. In order to monitor DPC repair in mammalian cells, we have devised a novel technique to identify DPCs and to track their fate, which we will employ to understand how the SUMO system detects DPCs and what determines replication-independent DPC repair pathway choice. Ultimately, we will build on these insights to investigate the nature of the endogenous substrates of DPC repair pathways.
Global-genome repair of DNA-protein crosslinks: lesion detection and pathway choice