Our research program focuses on understanding the interplay of protein structure, dynamics, and function, particularly in large macromolecular assemblies. Our current emphasis is the characterization of an essential protein complex that recognizes double-strand breaks in our DNA. Failure to repair this damaged DNA can lead to mutations and has been implicated in a variety of cancer types. To accomplish our goals, we utilize sophisticated solution state NMR spectroscopy techniques, which allow us to probe changes in protein structure and dynamics that occur as part of the functional cycle of the complex as well as changes that occur upon mutation of the complex. We couple this information with biochemical activity assays and in cell experiments, which report on function. Together, these data will provide a framework for understanding how changes in structure and dynamics of a protein complex choreograph complex functions.