FASEB SRC on Dynamic DNA Structures in Biology

Federation Of Amer Soc For Exper Biology, Bethesda MD

Investigators

Abstract

This proposal requests partial support for the FASEB Summer Research Conference on Dynamic DNA Structures in Biology, which will be held July 15-20, 2018, in Olean, NY. 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 helices, three- and four-stranded helices, 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. The cellular environment can also influence structure formation. Studies have confirmed that structure-prone DNA sequences are central to the normal functioning of the genome. Transitions in DNA structure are important for regulating the activation of transcription and the specialized recombination responsible for immunoglobulin class switching. Unscheduled transitions, however, can have pathological consequences. The expansion of structure-prone repeats underlies more than thirty hereditary neurological and developmental diseases in humans and 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 contribute to normal genetic processes and how they promote pathological outcomes such as genetic disease, cancer and aging. Our aims are to explore DNA structural transitions, 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 two opening keynote talks, eight morning/evening scientific sessions and informal afternoon poster sessions. New this year will be a session on genome editing. In addition, another new feature will be to involve early career scientists in the planning and content of ?meet the speaker? and career workshop discussions at the conference. One third of the talks will be chosen from submitted abstracts, with preference given to trainees and junior investigators. For many trainees, this will be the first opportunity to give a talk at a scientific meeting. 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.