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

拟议研究的目标是确定详细的 结构[并破译结构的序列依赖性] 双螺旋核酸，其中含有RNA和DNA 复式。主要重点将放在序列依赖性的 RNA：DNA杂合双链体和共价嵌合双链体结构 含有与DNA片段连接的杂交片段以及杂交片段 连接到RNA片段。这样的嵌合双链体是极其重要的。 在生物学中的DNA合成起始等过程中很重要， DNA的持续复制和逆转录病毒的生长， 它们的详细结构和序列的重要性知之甚少 在他们的功能。 我们最近已经证明，许多目前的想法， 混合双链体和混合双链体连接结构很可能 是晶体学的产物因此，所有拟议的结构 研究将在溶液中进行，使用高分辨率NMR 谱这些重要的生物结构直接决定了 不仅在现代分子生物学中， 生物学，但也将产生新的目标，专门抑制 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.