Canonical base

Figure 6.2 Structure of frans-activation response (TAR)-aptamer kissing complexes. The DNA D-04 (left) and the RNA aptamer R-06 (right) are shown in green. The crucial non-canonical base pairs are indicated in red (Collin et al 2000 Duconge and Toulme, 1999). (see Color Plate 5)...

The presence of ions not only affects canonical base pairs [22], but promotes the formation of triplexes and other non-canonical DNA structures [23]. The effects of these interactions span from modifications of the renaturation kinetics of thermally denaturated DNA [24] to the known anti-tumoral and mutagenic activity of cisplatin [25]. 

The theoretical. Sj nonradiative lifetimes by Markwick and Doltsinis [55] are in agreement with recent experimental observations [2, 79] which suggest that the canonical base pairs are extremely short-lived, the GC lifetime being of the order of 100 fs. This is also in accord with the scenario sketched by ab initio... 

The DNA lesion 8,5 -cyclo-2 -dG, formed by attack of hydroxyl radicals, contains damage to both base and sugar, and is therefore repaired by nucleotide excision repair enzymes, and is involved in diseases with defective nucleotide excision repair. A mass spectroscopic assay has been developed for the quantitation of the lesion after enzymatic separation of the 5 (R) and 5 (S) isomers. The thermodynamic stability of ODNs containing the oxidative lesion, 2-hydroxy-dA has been examined. It was shown that when the lesion was in the middle of a DNA duplex it behaved as a universal base, in that there was no dilference in Tm when opposite any of the canonical bases. On the other hand, when it was near the termini, there was a preference for base pairing with thymidine, but it also formed base pairs with other nucleotides which was sequence dependent. The extent of oxoprenylation by malondialdehyde or adenine propenal has been investigated in DNA, see (139). ssDNA was found to be more sensitive to oxoprenylation, and supercoiled-DNA more susceptible than linearised plasmid DNA. A variety of intercalators were used, some of which inhibit oxoprenylation, e.g. netropsin, whilst others, like ethidium bromide, caused enhanced oxoprenylation. 

The fact that U38, a conserved residue critical for catalytic activity in the L1L family, is docked into the ligation site and makes a canonical base pair with a constituent of the ligation site A51 in the docked conformation, whereas in the undocked conformation it is positioned 40 A away from the site, has led to the postulate that the former is more likely representative of a catalytically active state [64]. 

Through the successful incorporation of canonical bases to the PNA backbone,667-669 PNA oligomers were capable of forming WC duplexes with both DNA and RNA in antiparallel and parallel orientations (with the antiparallel orientation defined as the amino terminus of PNA and the 3 -end of the oligonucleotide at the same end). The antiparallel PNA DNA and PNA RNA duplexes have Tms +13.4 and +21.1 °C, respectively, higher than the parallel form. 

The resonance canonicals, based on the polarity C H+, correctly predict that the methyl group is activating to electrophilic substitution at the ortho and para carbon atoms in an aromatic ring. For SiH3 or SiMe3 the polarity is Si + H" and Si + C which leads to the resonance canonicals shown in equation 5. 

Base triads do, of course, occur in nucleic acid triplexes. However, tetraplex structures may also contain triads and in RNA structures triads often play a crucial role. Triplexes are formed by the interaction of a third strand in the major groove of a double helix. The duplex has to be composed of a homopurine-homopyrimidine sequence (piuine - R, pyrimidine - Y). The third strand can bind in a parallel or antiparallel orientation to one of the duplex strands. In parallel orientation, a homopyrimidine third strand binds to the homopurine strand of the duplex (YRY). This leads to the two canonical triads TAT and C+GC. Protonation of C (C+) at N3 is required for the formation of two H-bonds between C and G. Therefore, parallel triplexes are pH dependent. These structures have two canonical base triads TAT and C+GC. For an antiparallel orientation of the third strand relative to the binding duplex strand, a homopruine sequence is required that binds to the homopurine strand of the duplex (RRY). This results in the canonical triads GGC, AAT and TAT, where however the TAT triad is different to the corresponding triad in parallel triplexes. In addition to these standard triads, triplexes can also accommodate non-canonical base triads. Fig. 3 shows the two canonical triads C+GC and TAT in an intra-molecular triplex consisting of a DNA duplex and... 

Fig. 3. Canonical base triads TAT and C+GC in an intramolecular DNA triplex structure solved by NMR spectroscopy (PDB code ld3x). The triplex is linked by hexakis ethylene glycol units (EG) and has the sequence d(AGAGAGAA-(EG)6-TTCTCTCTt-(EG)6-TCTCTCTT). The triads have a non-cyclic topology III.l(2il2). In this and the following Figures the dotted lines indicate H-bonds.

This table takes only structures into account for which atomic coordinates have been deposited at the Protein Data Bank. Given polyads occur in several chain this indicated before the polyad. If polyads include bases from different chains the chain identifier is indicated in parenthesis. The numbering of bases involved in polyads is not given for regular triplex/tetr lex structures. The topology corresponds to the classification presented in Table 1. H-bonds between bases are indicated by dots. No difference is made between Watson-Crick and non-canonical base-base interactions. The base sequence follows the H-bond interaction pattern. For example, in the non-cyclic triad C.G.A C is bound to G and G to A. In more complex cases parentheses have been used. The H-bond analysis of nucleic acid structures has been performed with HBexplore. 

The major element of H-DNA is a triplex formed by one half of the insert adopting theb H form and by one of the two strands of the second half of the insert (Fig. 2e).Two major classes of triplexes are known-pyrimidine-purine-pyrimidine (PyPuPy) and pyrimidine-purine-purine (PyPuPu). Fig.3 shows the canonical base-triads entering these triplexes. 

Non-canonical base pairs The helices in RNA are generally short (lObp or less) and usually include unpaired nucleotides and non-canonical bps (bps other than G—C and A—U). Non-canonical bps present chemical groups in either the major or minor groove of the helix that can be used for unique tertiary interactions. 

GenBank of the NCBI, NIH Non-canonical base pair database Nucleic Acid Database (NDB) Oligonucleotide calculation PseudoBase ... 

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