FASEB SRC on Dynamic DNA Structures in Biology

描述（由申请人提供）：本提案要求部分支持将于2014年7月20-25日在伊利诺伊州伊塔斯卡举行的FASEB生物学动态DNA结构夏季研究会议。在DNA被发现后的几十年里，人们一直认为DNA是一种刚性的右旋双螺旋结构。这一信念被DNA结构更加动态的发现所动摇。事实上，DNA可以形成各种各样的构象，包括十字形、左旋螺旋、三链和四链螺旋、滑链结构等。最重要的是，重复的DNA序列，在基因组DNA中被过度代表，特别容易发生结构转变。双螺旋的瞬时变性促进了DNA结构的这些动态转变，发生在所有主要的DNA交易中，包括复制、转录和重组。在世界各地许多实验室进行的研究已经证实，结构倾向的DNA序列是基因组正常功能的核心，它们也是偶尔出现故障的原因。一个特别引人注目的例子是发现易于结构的DNA重复序列的扩展导致了三十多种人类遗传性神经和发育疾病。动态DNA结构也与许多人类癌症中观察到的易位有关。它们还参与正常的DNA过程，包括转录激活、抗原转换的调节和免疫应答所必需的DNA重组。出乎意料的是，这些DNA结构对纳米技术来说似乎是无价的，它们不同寻常的物理性质在纳米技术中得到了许多应用。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、如何促进正常遗传过程和病理发展（包括遗传疾病、癌症和衰老）的理解。具体目标是探索当前的理解，确定新的研究途径，定义促进动态DNA结构形成和分解的新机制，从而为维持基因组完整性提供治疗靶点，促进合作，并通过促进年轻科学家的参与来促进该领域的长期发展。为此目的，我们将

DESCRIPTION (provided by applicant): This proposal requests partial support for the FASEB Summer Research Conference on Dynamic DNA Structures in Biology, to be held at Itasca, Illinois, July 20-25, 2014. For decades after its discovery, DNA was believed to be a rigid, right-handed double helix. This belief was shaken by the findings that DNA structure is much more dynamic. In fact, DNA can form an enormous variety of conformations, including cruciform-like, left-handed helixes, three and four stranded helices, slip-stranded configurations, etc. Most importantly, repetitive DNA sequences, which are overrepresented in genomic DNA, are particularly prone to structural transitions. Transient denaturation of the double helix, which promotes these dynamic transitions in DNA structure, occurs during all major DNA transactions, including replication, transcription, and recombination. Studies conducted in many labs worldwide have confirmed that structure-prone DNA sequences are central to the normal functioning of the genome, and they are also responsible for its occasional malfunctioning. One particularly striking example is the discovery that expansions of structure-prone DNA repeats leads to more than thirty hereditary neurological and developmental diseases in humans. Dynamic DNA structures are also associated with translocations observed in many human cancers. They are also involved in regular DNA processes including transcriptional activation, regulation of antigenic switching, and DNA recombination essential to the immune response. In an unexpected twist, these DNA structures appeared to be invaluable for nanotechnology, where their unusual physical properties find numerous applications. 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 to pathological developments, including genetic disease, cancer and aging. The specific aims are to explore current understanding, to identify new avenues of investigation, to define novel mechanisms that promote formation and resolution of dynamic DNA structures and, thus, offer therapeutic targets for maintenance of genomic integrity, to stimulate collaborations, and to foster the long-term development of this area by promoting participation of junior scientists. To that end, we will convene 33 speakers and discussion leaders and more than 100 participants for five intense and highly interactive days of science. The program will include a keynote and eight sessions, entitled: (1) Expandable DNA Repeats and Human Disease; (2) Chromosomal Fragility; (3) Transcription and Its Collisions with Replication; (4) Repeat-Induced Mutagenesis; (5) DNA Gymnastics in Recombination; (6) Recurrent and Non- Recurrent Chromosomal Rearrangements in Human Disease; (7) G4 DNA in the Genome; (8) Nano-DNA Structures. Each session will include two-to-four short talks by students, postdocs, and newly independent investigators, and three afternoon poster sessions will permit the attendees to present and discuss their newest results. The significance of this conference is that it uniquely propels research by bringing together investigators with a common focus but varied backgrounds, expertise and experimental approaches, thus, enabling research to progress more rapidly. The biomedical relatedness is in the importance of dynamic DNA structures in normal nuclear functions and as the cause of genomic pathologies that result in genetic disease.