PHYSICAL CHEMISTRY OF RECOMBINATIONAL INTERMEDIATES

描述：基因重组普遍发生在生物体中， 从病毒到人类。 大部分的DNA代谢都致力于确保 稳定性是其作为遗传物质所必需的，但重组 为物种适应变化提供了必要的灵活性 环境. 其关键特征是两段DNA的相互作用， 产生了新的遗传物质， 分子。 重组的结果包括病毒整合到 从原核噬菌体到逆转录病毒，如 艾滋病毒，在人类。 基因换位，免疫系统的发展 系统，以及人类基因库的多样化都是由于 重组过程 腐败不仅仅是一种被动的现象， 是遗传学家用来修改实验物种基因的工具。 这项工作的目标是了解结构，动力学和 DNA分子参与遗传重组的热力学。 博士 Seeman专注于DNA模型系统，可以设计和合成， 实验室 这些分子中的关键是霍利迪结， 是一个四股分支的中间体，但西曼博士经常使用 分子与两个路口，以获得构象纯度;这些平行 双交换分子是减数分裂中间体。 两种异构化 与遗传后果有关的是霍利迪路口，分支 迁移和交叉异构化。 西曼医生会问三个问题 关于分支迁移：（1）所有迁移位置的可能性相等吗？ (2)反平行霍利迪结分支会迁移吗？ (3)Do parallel 双交叉分子分支迁移：他会问两个问题， 交叉异构化：（1）它真的是一个物理过程吗？ (2)可以 Holliday连接辫，这与它在分子中的作用机制有关 平行领域？ 他还试图建立 分支位点和Holliday切割所需的序列 RuvC resolvase的连接。 西曼博士发现了一种新的DNA基序， 他认为这可能支持在同源重组中寻找同源性。 他将用实验来挑战这一建议， 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。 它会产生混凝土 这些不寻常的DNA分子结构和物理知识。 的 最终目标是提供对自然重组的分子控制 现象和过度重组的干预， 实验室和明天的诊所。

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.