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

DNA/RNA 领域功能分子设计的结构基础

基本信息

批准号：
12480177
负责人：
TAKENAKA Akio
金额：
$ 9.41万
依托单位：
TOKYO INSTITUTE OF TECHNOLOGY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12480177/
关键词：
DNA RNA world Functional nucleic acid Damaged DNA X-Ray analysis I-motif of G-quartets Octa-stranded helix Base-paired parallel duplex base-intercalated duplex 平行二重らせん 5-ホルミルウラシル 5-ホルミルシトシンシュードウリジンマキシザイム RNA リボザイムヘアピンDNA

项目摘要

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

该项目已经成功地进行了并揭示了新型的核酸结构，包括用于突变的受损DNA、RNA中的修饰核苷酸、平行链双链、凸入双链、手间和手内口袋相互作用以及碱基嵌入双链。在不同的条件下，通过改变X、Y和Z处的残基来研究带有d(GcGXYZgc)的DNA片段。已经发现，即使当它在X和Y处发生突变时，该序列也总是倾向于形成碱基嵌入的双链。然而，除了Z位的A外，含有核苷酸的序列不能采用碱基插层双链。碱基插层双链与沃森和克里克50年前提出的标准双螺旋有很大的不同。此外，我们还发现三个碱基插层双链在六价钴离子周围聚集形成一个六链螺旋。当阳离子被钾阳离子取代时，碎片聚集形成八链He…更多的里克斯(八倍体)。此外，在稍高的钾浓度下(在生理条件下)，八层复合体只分裂成两半。我们发现，具有gcGA[G]_1Agc序列的DNA片段首先形成碱基插层双链，可以缔合形成四链，最后两个四链结合形成八链。最近的基因组分析显示，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。上面描述的八链构型表明，重复序列可以通过双希腊键基序折叠形成簇。这些结果在ASCA-2003会议上公布，并被国际结晶学联合会授予IUCr奖。由于这个项目中发现的几个结构对于理解生物现象和开发功能核酸的某些目的是有用的，这个项目应该扩大到进一步的研究。较少