PHYSICAL CHEMISTRY OF RECOMBINATIONAL INTERMEDIATES

描述：基因重组普遍存在于生物体内， 从病毒到人类。DNA新陈代谢的很大一部分是为了确保 作为遗传物质发挥作用所需的稳定性，但重组 为物种适应变化提供了必要的灵活性 环境。它的主要特征是两个DNA片段相互作用 产生新的遗传物质，可能包含两个相互作用的片段 分子。重组的后果包括病毒整合在 从原核噬菌体到逆转录病毒的物种，如 艾滋病毒，在人类身上。基因易位，免疫的发展 制度，以及人类基因库的多样化都是由 重组过程。重组不仅仅是一种被动的现象；它 是遗传学家用来修改实验物种基因的工具。 这项工作的目标是理解结构、动力学和 参与基因重组的DNA分子的热力学。Dr。 Seeman专注于DNA模型系统，这些系统可以在 实验室。这些分子中的关键是Holliday连接，它 是一种四链分支中间体，但西曼博士经常使用 具有两个连接以获得构象纯度的分子；这些平行的 双交叉分子是减数分裂的中间产物。两种异构化反应 具有遗传后果的基因与Holliday连接、分支相关 迁移和交叉异构化。西曼博士将问三个问题 关于分支机构迁移：(1)所有迁移职位的可能性都一样吗？ (2)反平行Holliday连接分支迁移吗？(3)平行 双交叉分子分支迁移：他将问两个问题 交叉异构化：(1)它真的是一个物理过程吗？(2)可以 Holliday结编织，这与其在分子中的机制有关 使用平行域？他还寻求建立两国之间的关系 Holliday裂解所需的分支点位置和序列 RuvC解析器连接。西曼博士发现了一种新的DNA基序 他提出，可能支持在同源重组中寻找同源性。 他将通过实验来挑战这一建议，以确定其特征 结构及其与RecA的相互作用。 即将进行的研究将回答有关DNA的关键问题 参与重组的分子。它将产生混凝土 关于这些不寻常的DNA分子的结构和物理知识。这个 最终目标是提供对自然重组的分子控制 现象和今天在美国进行的重组干预 实验室，明天在诊所。

DESCRIPTION: Genetic recombination occurs universally in living organisms, from viruses to humans. Much of DNA metabolism is devoted to ensuring the stability necessary for its role as genetic material, but recombination affords the flexibility necessary for species to adapt to changing environments. Its key feature is the interaction of two pieces of DNA to yield new genetic material that may incorporate segments of both interacting molecules. The consequences of recombination include viral integration in species ranging from prokaryotic bacteriophages to retroviruses, such as HIV, in humans. Genetic transposition, the development of the immune system, and the diversification of human gene pools all result from recombination processes. Recombination is not just a passive phenomenon; it is a tool used by geneticists to modify the genes of experimental species. The goals of this work are to understand the structure, dynamics and thermodynamics of DNA molecules involved in genetic recombination. Dr. Seeman focuses on DNA model systems that can be designed and synthesized in the laboratory. Key among these molecules is the Holliday junction, which is a four-stranded branched intermediate, but Dr. Seeman often uses molecules with two junctions to obtain conformational purity; these parallel double crossover molecules are meiotic intermediates. Two isomerizations with genetic consequences are associated with Holliday junctions, branch migration and crossover isomerization. Dr. Seeman will ask three questions about branch migration: (1) Are all migratory positions equally likely? (2) Do antiparallel Holliday junctions branch migrate? (3) Do parallel double crossover molecules branch migrate: He will ask two questions about crossover isomerization: (1) Is it really a physical process? (2) Can Holliday junctions braid, which is related to its mechanism in molecules with parallel domains? He also seek to establish the relationship between the site of the branch point and sequences required for cleavage of Holliday junctions by RuvC resolvase. Dr. Seeman has discovered a new DNA motif that he suggests may support the search for homology in homologous recombination. He will challenge this suggestion with experiments to characterize its structure and its interactions with RecA. The research to be performed will answer key questions about the DNA molecules that are involved in recombination. It will yield concrete structural and physical knowledge about these unusual DNA molecules. The ultimate goal is to provide molecular control over natural recombination phenomena and over recombinational interventions done today in the laboratory and tomorrow in the clinic.