Final Report Summary - DDRREAM (DNA-Damage responses: Regulation and mechanisms)
The cells in our bodies are constantly being exposed to agents that damage our DNA. Cells have evolved a complex system, termed the DNA damage response (DDR) that detects DNA damage, signals its presence to the cell and sets about repairing this damage. The DDR is crucial for cell survival and to guard against cancer. The aims of this project have been to identify important new DDR proteins and DDR modulators; provide insights into how these proteins function; and to understand how the modification of these proteins and the DNA at sites of damage affect DNA repair and other cellular events. To this end, we have identified a number of proteins of the Ubiquitin and SUMO systems (types of protein modifications that affect protein function) that control events of the DDR and shed new light on how this dynamic process is regulated at the molecular level. In the course of this project we have explored and embraced novel methodologies including high-resolution microscopy, chemical genetics and cutting edge gene editing technologies to help us better understand and define DDR processes.