HELICAL RNA, RNA/DNA HYBRIDS AND DNA/RNA JUNCTIONS

螺旋 RNA、RNA/DNA 杂交体和 DNA/RNA 连接

• 批准号: 2181714
• 负责人: BRIAN R REID
• 金额: $ 17.03万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2181714
• 关键词: DNA; DNA replication; RNA; RNA biosynthesis; chemical structure function; covalent bond; deoxyribonucleotides; hydrogen bond; nuclear magnetic resonance spectroscopy; nucleic acid denaturation; nucleic acid sequence; nucleic acid structure; ribonucleotides

The objectives of the proposed research are to determine the detailed structure [and to decipher the sequence-dependence of the structure] of double helical nucleic acids containing both RNA and DNA in the same duplex. Major emphasis will be placed on the sequence dependence of the structure of RNA:DNA hybrid duplexes and on covalent chimeric duplexes containing hybrid segments joined to DNA segments as well as hybrid segments joined to RNA segments. Such chimeric duplexes are extremely important in biology in such processes as the initiation of DNA synthesis, the continued replication of DNA, and the growth of retroviruses - yet little is known of their detailed structure and the importance of sequence on their function. We have recently demonstrated that many current ideas concerning the structure of hybrid duplexes and hybrid duplex junctions are very likely to be crystallographic artifacts. Hence all of the proposed structural studies will be carried out in solution using high-resolution NMR spectroscopy. These biologically important structures determined directly in solution will have widespread importance not only in modern molecular biology but will also generate new targets for specifically inhibiting the life-cycle of retroviruses.

拟议研究的目标是确定详细的 结构[并破译结构的序列依赖性] 双螺旋核酸在相同的同时包含RNA和DNA 双工。重点将放在序列依赖性上 RNA的结构：DNA混合双链体和共价嵌合双工 包含连接到DNA段的混合段以及混合动力 段连接到RNA段。这样的嵌合双工非常 在生物学中重要 DNA的持续复制和逆转录病毒的生长 - 然而 对它们的详细结构和序列的重要性知之甚少 在他们的功能上。 我们最近证明了许多关于 混合双链体和杂化双工结构的结构很可能很可能 是晶体图。因此所有提议的结构 研究将在溶液中使用高分辨率NMR进行 光谱法。这些直接确定的生物学上重要的结构 在解决方案中，不仅在现代分子中具有广泛的重要性 生物学，但也将产生新的目标，以特别抑制 逆转录病毒的生命周期。