This proposal requests partial support for the FASEB Science Research Conference on Dynamic DNA Structures in Biology, which will be held July 10-15, 2016, in Saxtons River, VT. For decades after its discovery, DNA was believed to be a rigid, right-handed double helix. It is now appreciated, however, that DNA is highly dynamic molecule and can assume an enormous variety of conformations such as cruciforms, left-handed helixes, three- and four-stranded helixes, and slip-stranded configurations. Repetitive DNA sequences, which are overrepresented in genomic DNA, are particularly prone to such structural transitions. The transient denaturation of the double helix that occurs during most DNA transactions (transcription, replication and recombination) also promotes dynamic transitions in DNA structure. Studies conducted in many labs worldwide have confirmed that structure-prone DNA sequences are central to the normal functioning of the genome. Transitions in DNA structure, for example, are important for regulating the activation of transcription and the specialized recombination responsible for immunoglobulin class switching. Unscheduled transitions, however, can have pathological consequences. Of particular significance, the expansion of structure-prone repeats underlies more than thirty hereditary neurological and developmental diseases in humans. Furthermore, dynamic DNA structures are associated with genome rearrangements observed in many human cancers. The long-term objective of this Conference is to enhance our understanding of how dynamic DNA structures form, how they are resolved, how they contribute to normal genetic processes and how they promote pathological outcomes such as genetic disease, cancer and aging.
The specific aims are to explore current understanding of DNA structural transitions, to identify new avenues of investigation, to define novel mechanisms that promote formation and resolution of dynamic DNA structures, to stimulate collaborations, and to foster the long-term development of this important area by promoting participation of junior scientists. To that end, we will convene ~100 participants for five intense and highly interactive days of science. The program will include an opening keynote address, eight morning/evening scientific sessions and informal afternoon poster sessions. In addition to invited speakers, each scientific session will include four short talks chosen from submitted abstracts, with preference given to trainees and junior investigators. The significance and strength of this Conference is that it uniquely brings together investigators with a common focus on dynamic DNA transitions, but who have highly varied backgrounds, expertise and experimental approaches.
DNA is a highly dynamic molecule that can adopt of variety of different structures. Although such structural transitions are important in normal genetic processes, their unscheduled formation can be pathological, resulting in hereditary diseases, cancer or aging. This conference will focus on the formation, resolution and consequences of dynamic DNA structures, which is the key to understanding the origin of human disease and developing appropriate therapeutics.
