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Nick Lakin

Detection, Signalling and Repair of DNA Damage

Our group aims to understand how cells repair damage to DNA, how this maintains the integrity of the genetic material, and how dysfunction of these pathways leads to a variety of age related pathologies, including cancer. Cells are continually exposed to a variety of agents that cause DNA damage and a critical response to this stress is to signal the damage in order to coordinate and regulate its repair. We are interested in this process, with specific reference to how a family of enzymes called poly (ADP-ribose) polymerases (PARPs) regulate genome stability through post-translationally modifying proteins by a process called ADP-ribosylation. By exploiting cutting-edge genome engineering, cell imaging, proteomic and genetic screening techniques, we aim to elucidate how PARPs recognise DNA damage, what proteins they ADP-ribosylate, and how this regulates the DNA repair process. This work will not only decipher the molecular basis of the cellular response to DNA damage, but also provide critical information in targeting these pathways to treat a variety of age related diseases, including cancer.