Structural basis for design of functional molecules in the DNA/RNA world

该项目已成功实施，并揭示了新型核酸结构，包括用于诱变的DNA损伤，RNA中的核苷酸修饰，平行链双链，凸出双链，手间和手内口袋相互作用以及碱基插入双链。通过在不同条件下改变X、Y、Z位点的残基，研究了含d（gcGXYZgc）的DNA片段。已经发现，即使在X和Y位点发生突变，该序列也总是倾向于形成碱基插入的双工。但是，Z处除A外含有核苷酸的序列不能采用碱基插入双工。碱基嵌层双螺旋结构与50年前由沃森和克里克提出的标准双螺旋结构完全不同。此外，我们发现三个碱基插入的双链在钴离子周围组装形成六链螺旋（hexaplex）。当阳离子被钾离子取代时，碎片组装形成一个八链（八链）。此外，在稍高的钾浓度下（在生理条件下），八联体被分成两半。我们发现，序列为gcGA[G]_1Agc的DNA片段首先形成碱基插入双链，并结合形成四联体，最后这两个四联体结合形成八联体。最近的基因组分析表明，人类基因组中含有大量的重复序列，超过50%，其中与上述片段相似的特定序列在VNTR中重复了8次。上述八联体的形成表明，重复序列可以通过双希腊键基序折叠形成一个簇。这些成果在AsCA-2003年会议上发表，并获得了国际晶体学联合会颁发的IUCr奖。由于本项目中发现的几个结构对某些目的的理解生物现象和开发功能性核酸是有用的，因此本项目应扩展到进一步的研究。少

The project has been successfully performed and revealed the new types of nucleic acid structures, including damaged DNA for mutagenesis, modified nucleotides in RNA, parallel-stranded duplex, bulged-in duplex, inter-and intra-hand-in pocked interaction and base-intercalated duplexes. DNA fragments with d(gcGXYZgc) were investigated by changing the residue at X, Y and Z under different conditions. It has been found that even when it is mutated at X and Y, the sequence always prefer to form a base-intercalated duplex. However, the sequences containing nucleotide except A at Z cannot adopt the base-intercalated duplex. The base-intercalated duplex is quit different from the standard double helix, which was proposed by Watson and Crick 50 years ago. In addition, we found that three base-intercalated duplexes assemble to form a hexa-stranded helix (hexaplex) around cobalt-hexamine cations. When the cation was replace with potassium cation, the fragments assemble to form an octa-stranded he … More lix (octaplex). Furthermore at slightly higher potassium concentration (within physiological conditions), the octaplex is split into just two halves. We have discovered that DNA fragments with sequence gcGA[G]_1Agc form at first base-intercalated duplexes which can associate to form a quadruplex, and finally the two quadruplexes associate to form an octaplex. Recent genome analyses revealed that the human genome contains a huge amount of repetitive sequence's over 50 %, in which a specific sequence similar to the above fragment has been found to be repeated by eight times in VNTR. The octaplex formation described above suggests that the repetitive sequence can fold to form a cluster by double Greek-Key motif. These results were presented in AsCA-2003 meeting and awarded the IUCr prize from International Union of Crystallography. As the several structures found in this project are useful for certain purposes to understand biological phenomena and to develop functional nucleic acids, this project should be extended to further investigations. Less