Genome stability is the foundation upon which all cellular and organismal processes depend. This conference will grapple with the intricate array of biochemical reactions orchestrated by the cell to replicate, repair and segregate chromosomes accurately despite constant threats from spontaneous and environmentally-induced damage. Defects in these reactions lead to genomic instability, a confirmed driver of cancer and degenerative diseases. Fascinating and therapeutically crucial questions remain about the mechanisms underlying chromosome stability, and cross-disciplinary approaches are required to address them. How do epigenetic chromatin marks influence repair of underlying DNA sequences, and how can we predict the effects of chemotherapeutic agents that alter such marks? To what extent is the nucleus organized into subdomains with distinct functions; how are these subdomains altered when cells move or differentiate? How are the myriad helicases, nucleases and polymerases coordinated to safeguard genome stability, why are these molecules often mutated in human disease, and how can we ameliorate the effects of such mutations? What is the array of strategies available to cancer cells as they achieve unlimited proliferation? This conference has a history of bringing together investigators from diverse subfields who otherwise rarely meet. Cutting-edge concepts in translational, genomic, cellular, molecular, RNA and structural biology will be dissected to take the conversation to unprecedented levels of depth and breadth. The concurrent conference on “DNA Replication and Recombination” will provide additional opportunities for cross-talk. Both conferences are committed to nurturing interactions among longtime experts in the field with students, postdocs and investigators new to the field.