FASEB SRC on Dynamic DNA Structures

 描述(由申请人提供)：本提案请求部分支持将于2016年7月10日至15日在佛蒙特州萨克斯顿河举行的FASEB生物学动态DNA结构科学研究会议。在发现DNA后的几十年里，人们一直认为DNA是一个刚性的右旋双螺旋结构。然而，现在人们意识到，DNA是高度动态的分子，可以呈现出各种各样的构象，如十字形、左手螺旋、三链和四链螺旋，以及滑链构型。在基因组DNA中过度表达的重复DNA序列特别容易发生这样的结构转变。在大多数DNA交易(转录、复制和重组)中发生的双螺旋的瞬时变性也促进了DNA结构的动态转变。在世界各地的许多实验室进行的研究已经证实，易于结构的DNA序列是基因组正常功能的核心。例如，DNA结构的转变对于调节转录的激活和负责免疫球蛋白类别转换的专门化重组非常重要。然而，计划外的过渡可能会产生病理性的后果。具有特别重要意义的是，结构倾向重复序列的扩展是人类30多种遗传性神经和发育疾病的基础。此外，在许多人类癌症中观察到的动态DNA结构与基因组重排有关。本次会议的长期目标是加强我们对动态DNA结构如何形成、如何分解、它们如何促进正常遗传过程以及它们如何促进遗传病、癌症和衰老等病理结果的理解。其具体目的是探索当前对DNA结构转变的理解，确定新的研究途径，确定促进动态DNA结构形成和分解的新机制，促进合作，并通过促进初级科学家的参与促进这一重要领域的长期发展。为此，我们将召集约100名参与者，进行五天紧张和高度互动的科学活动。该计划将包括开幕主旨演讲、八个上午/晚上的科学会议和下午的非正式海报会议。除了被邀请的演讲者外，每个科学会议还将包括从提交的摘要中选择的四个简短演讲，受训人员和初级调查人员优先考虑。本会议的意义和力量在于，它以独特的方式将 研究人员共同关注动态DNA过渡，但具有非常不同的背景、专业知识和实验方法。

 DESCRIPTION (provided by applicant): 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.