Читать книгу Chemistry and Biology of Non-canonical Nucleic Acids - Naoki Sugimoto - Страница 41

1 Learn interactions in nucleic acid structures.

Nucleobases can adopt syn and anti conformations in their glycosidic bond angle. In addition, in the ribose conformation, there are C2′-end- and C3′-end-type conformations, which are found in the B-form and A-form duplexes, respectively. The flexible feature of the strands allows formation of various base pair patterns and their dynamic fluctuations. In the case of DNA, mismatched base pairs can be formed by incorporation of incorrect substrate during replication reaction. Each mismatched base pair exhibits different thermodynamic stability, in which several types of mismatched base pairs are comparable with standard Watson–Crick base pairs. This is because not only hydrogen bonding between nucleobases but also stacking interactions are important factors that determine the stability.

1 Understand structure polymorphisms of nucleic acids.

Canonical right-handed duplex with Watson–Crick base pairs is one of the polymorphic structures of nucleic acids. DNA varies in its backbone conformation, such as Z-type duplex, multi-stranded helix, and cruciform depending on the primary sequence. In the case of RNA, since the backbone is intrinsically single stranded, it forms a variety of higher-order structures compared with DNA. Various proteins that recognize these non-canonical nucleic acid structures are present in cells. These proteins are usually involved in modulation of gene expression. It is likely that the non-canonical higher-order structures and their polymorphisms play roles in altering the expression of genetic information, whereas the canonical duplex structure plays a role in retaining genetic information. In Chapters 5–8, reactions of transcription, translation, and replication including telomere region that are affected by the non-canonical nucleic acid structures are described.

1 Study differences in conformational properties between DNA and RNA.

As described above, RNAs form a variety of higher-order structures compared with DNA. Formation of hydrogen bonds via the 2′-hydroxyl group, which is a unique element of RNA, plays an important role in the higher-order structures. Non-base-pairing regions, such as bulges and loops, not only alter the helicity of stem regions but also allow interaction in distant regions via characteristic tertiary interaction motifs such as kissing loop, T-loop, GNRA tetraloop receptor, and pseudoknot that contribute to shaping their overall structure. In addition, reinforcement for compacting the RNA structure against electrostatic repulsion between phosphates is necessary in order to form the complex RNA structures. Interactions forming hydrogen bonds in various patterns such as observed in A-minor motifs and ribose zippers would contribute greatly to support the higher order structures.