The DNA damage response (DDR) is a complex signaling network including cell cycle checkpoints, DNA repair and DNA-damage tolerance pathways. The DDR is affected by, and impacts on, many cellular components and processes, including chromatin structure, DNA replication, transcription and cell cycle progression. Failure to properly respond to DNA damage leads to genomic instability, an underlining cause of various human syndromes and also associated with many age-related diseases, particularly cancer. Notably, it is becoming clear that the DDR is an attractive therapeutic target for cancer and other disease areas. This EMBO Conference will cover all the above topics in ways that will link detailed molecular mechanisms of the DDR and associated processes to human ageing, disease and therapeutic applications.