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

拟议研究的目标是确定详细的 结构[并破译结构的序列相关性] 同时含有RNA和DNA的双螺旋核酸 双面打印。主要的重点将放在序列相关性上 RNA：DNA杂合双链和共价嵌合双链的结构 包含连接到DNA片段的杂交片段以及杂交种 片段连接到RNA片段。这种嵌合的双链是非常 在生物学中的重要作用，如DNA合成的启动， DNA的持续复制和逆转录病毒的生长-至今 人们对它们的详细结构和序列的重要性知之甚少 关于他们的功能。 我们最近已经证明了许多当前关于 杂合双链和杂合双链的结构很可能 是结晶学的文物。因此，所有拟议的结构 将使用高分辨率核磁共振在溶液中进行研究 光谱学。这些生物上重要的结构直接决定了 在溶液中不仅在现代分子中具有广泛的重要性 生物学，但也将产生新的靶点，特别是抑制 逆转录病毒的生命周期。

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.