STRUCTURES OF DNA AND RNA QUADRUPLEXES

富含嘌呤的核苷酸序列与许多 重要的生物过程。这些包括在真核生物中的作用。 染色体复制、基因调控、减数分裂与逆转录病毒 复制周期。在过去的几年里，情况变得很明显 这些功能中至少有一些与 富嘌呤寡核苷酸形成四链结构的能力 由G四重奏稳定下来的。在这里提出的工作中，核磁共振 光谱学将被用来确定高分辨率溶液 几种已知的DNA和RNA寡核苷酸的结构，或 怀疑，在生理条件下形成G-四重奏。这个 选择用于研究的寡核苷酸旨在回答特定的 关于DNA和RNA序列高阶结构的几个问题 分别在端粒和逆转录病毒基因组中发现。从长远来看 DNA研究的目标是了解细胞的正常功能 端粒在染色体复制和细胞分裂中的作用核糖核酸研究 旨在加深对逆转录病毒的了解 复制周期与潜在抗病毒靶点的确定 探员们。

Purine-rich nucleotide sequences have been implicated in a number of important biological processes. These include roles in eucaryotic chromosome replication, gene regulation, meiosis and the retrovirus replication cycle. Over the past several years it has become clear that at least some of these functions are intimately connected with the ability for purine-rich oligonucleotides to form quadruplex structures that are stabilized by G-quartets. In the work proposed here, NMR spectroscopy will be used to determine the high resolution solution structures of several DNA and RNA oligonucleotides which are known, or suspected to, form G-quartets under physiological conditions. The oligonucleotides selected for study are intended to answer specific questions related the higher order structures of DNA and RNA sequences found in telomeres and retrovirus genomes, respectively. The long term goals of the DNA studies are to understand the normal functionality of telomeres in chromosome replication and cell division. The RNA studies are directed towards an increased understanding of the retrovirus replication cycle and identification of promising targets for anti-viral agents.