Watson—Crick duplexes

Previous work has suggested that aminoglycoside specificity may occur in nucleic acid forms that display features characteristic of an A-type conformation (RNA triplex, DNA-RNA hybrid duplex,RNA duplex, DNA triplex, A-form DNA duplex, and DNA tetraplex ), rather than in naturally occurring RNA. However, conflicting results have been reported regarding the conformation of the triplex and of the Watson-Crick duplex within these triplexes. Both... 

Figure 5-34 (A) Two conformations of a segment of the yeast phenylalanine tRNA gene. The segment shown codes for the 3 end of the tRNA molecule shown in Fig. 5-30, including the T /C loop. (B) Formation of H-DNA (Fig. 5-24) proposed for a sequence in plasmid pGG32. The major element of the structure is the triplex, which is formed from the Watson-Crick duplex ( ) associated with the homopyrimidine loop through Hoogsteen base pairing (o, +). One of the two possible "isomeric" forms is shown. See Mirkin et al.378...

Steinbeck, C., and Richert, C. 1998. The role of ionic backbones in RNA structure An unusually stable non-Watson-Crick duplex of a nonionic analog in an apolar medium. J. Am. Chem. Soc. 120 11576-11580. 

The extra hydrogen-bonding sites can, however, also form further base pairs, as observed for poly(A) poly(U). In the Watson-Crick A-U pair, one of the adenine N(6)-H donors and the N(7) acceptor are still free and can form another A-U pair of the Hoogsteen type (Fig. 16.16). This is in fact observed if the Watson-Crick duplex poly(A) poly(U) is exposed to high salt conditions, it disproportionates to form a triplex poly(A)-2poly(U) and a single strand poly(A) [539] ... 

Because the glycosyl links and the associated sugar-phosphate backbone are related, in the Watson-Crick duplex, by a pseudodyad perpendicular to the helix axis, the two strands are oriented antiparallel. They are parallel in the Hoogsteen duplex because the glycosyl links are related by rotation about the helix axis. 

The double helix formed by poly(G) poly(C) does not disproportionate. The reason is that it forms an extremely stable Watson-Crick duplex and that the Hoogsteen base pair could only form if poly(C) were protonated (legend to Fig. 16.16). 

Triple-helix formation by G-rich oligonncleotides is supported by Mg + but strongly inhibited by physiological concentrations of certain monovalent cations, especially K+, most likely dne to oligonncleotide self-association in competitive structures such as guanine-quadruplexes. " Variation of the cation enviromnent can differentially promote the assembly of multistranded nncleic acid structural alternatives. For example, by specifically counteracting the induction/stabilization of quadruplex structures by potassium ions, certain divalent ions (i.e. Mn +, Co +, and Ni + but not Mg +) at low millimolar concentrations allow triplex formation in the presence of 150mMK+. In contrast, certain mono- and divalent metal ions can promote the transition from Watson-Crick duplexes to G4 quadruplex structures relatively efficiently K" " > Ca + >... 

PNAs and regular DNA both contain repeating six-bond units between the base attachments (in bold). The former are found to form very stable Watson-Crick duplexes with DNA and RNA. " ... 

Self Association of Watson-Crick Duplex Sequences to Form Tetraplexes... 

G-rich sequences that fold into G-quadruplex structures can, of course, form Watson-Crick duplexes with their complementary C-rich strands. The formation of G-quadruplex or duplex structures within the cell will therefore depend... 

Fig. 4. Stereo view of the Watson-Crick duplex of the oligomer d( i 111 TCGCGCGCG) showing a B/Z junction in which the terminal four CG base pairs in the Z form bend toward the minor groove.

Outline the basic process by which a Watson-Crick duplex replicates to give two identical daughter duplexes. Explain the reasons for the accuracy of the process. 

Figure 53. Model of a p-RNA Watson-Crick duplex. Strand (mentation is strictly expected to be antiparallel, due to the strong inclination of the backlxme and base pair axes.

Thermodynamic and kinetic data snggest that quadruplex stability depends on a nnmber of factors, including the type of structure adopted by the DNA strand (or strands), strand sequence, the size of intervening loops, base and phosphate modifications, pH and the presence of cations [19]. Small molecules may stabilize quadraplex DNA (or facihtate DNA folding into quadruplex structures) due to shifting the competitive equilibrium between the single-stranded or Watson-Crick duplex and quadruplex DNA towards the latter form [19,20]. Inhibition activity of G4 ligands depends mainly on the stability of their complexes with telomeric DNA quadruplexes. 

However, preliminary results indicate a more complex binding stoichiometry than for a simple Watson-Crick duplex. The fact that there is no specific binding to RNA was explained by the authors by modeling the effective backbone length that matches DNA rather than RNA In the morpholino-type analogs, the Cl -Cr distance is shortened by 1.3 A in comparison with RNA in the A-conformatiwi, but only by 0.8 A compared to the natural phosphodiester linkage of DNA in the B-conformation. 

Besides the canonical triplexes formed, for example, between thymine and the adenine-thymine base pair and cytosine and the guanine-cytosine base pair other combinations have been suggested to form stable triplexes, e.g. G-TA, G-GC and T-GC [43], The stability of triplexes depends on pH, ionic strength, temperature, and, in cases where the Watson-Crick duplex is part of a plasmid DNA, it depends on supercoil density [44]. 

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