Penny Jeggo has focused on studying the response to DNA damage in mammalian cells and its contribution to human health. A major focus has been in studying the response to DNA double strand breaks (DSBs), including pathways of DSB repair, the signalling response to DSBs and, more recently, the interplay between the repair pathways and the signalling response. Penny played a key role in identifying the components of DNA-PK (Ku and DNA-PKcs) as being important components of DNA non-homologous end-joining (NHEJ), the major DSB repair pathway in mammalian cells, representing the first identification of genes having a major role in promoting radioresistance.