ABSTRACT Support is requested for a Keystone Symposia conference entitled Genomic Instability and DNA Repair, organized by Drs. Katharina Schlacher, Irene Chiolo and Ralph Scully. The conference will be held in Whistler, BC, Canada from March 19-23, 2023. DNA replication and repair are critical processes that initiate, orchestrate, and affect a broad range of fundamental physiological reactions, ultimately promoting cell division, genome stability, and proper cellular physiology. The field of genome stability is rich in mechanistic understanding that directly led to development of small molecule inhibitors such as PARP inhibitors, now used standardly in the clinic as anti-cancer agents. Nuclear genome stability actors, however, do not act in a vacuum, but interact, communicate and collaborate with diverse intrinsic and extrinsic cellular processes. The field is at the cusp of the next level of understanding of how diverse cellular and physiological reactions directly work together with genome stability mechanisms on a molecular level and how to use this understanding to develop new treatment strategies against human diseases. The control and governance of inflammatory and immune signaling reactions as it relates to replication and chromatin reactions in particular is a potentially potent cutting-edge connection for the field, given the importance of these reactions during immunotherapy of cancer. This is enabled specifically by the continued development of single molecule targeting agents, which have arise from the strong molecular understanding of the field. The knowledge of how to control and direct inflammatory signaling will propel our understanding of how to control diseases beyond cancer. This includes viral infections, which are of particular relevance to public health during the recent pandemic. This Keystone Symposia conference will highlight the latest advances and emerging concepts in the field, aspiring to prompt rich discussions especially focused on implications for medical biology, disease and treatment strategies. This conference focusing on DNA replication and repair will be held jointly with a conference on Precision Genome Engineering, providing outstanding opportunities for cross-fertilization between these two complementary fields.