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

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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