DNA base tetrads

Stability and Structures of the DNA Base Tetrads A Role of Metal Ions... 

Challenging for both experimental and theoretical investigation is the tetrads form by different DNA basis. Among mixed DNA base tetrads studied are TATA, AGAG, GCGC, UAUA, and T+AT+A, where T+ represents the 5-bromouracil. 

Nucleic acids can form complex structures that consist of more than two strands. Recently, the interest in structures and functions of the DNA bases polyads has significantly increased. It has been shown that guanine tetrads are vital components of many biologically important processes. 

Computational studies could shed light on molecular structures and properties of such systems. A series of tetrads of DNA bases has been recently investigated in our laboratory. Ab initio, nonempirical quantum chemical method has been used in these studies. The considered structures reveal different conformational preferences of DNA bases. They have also one common feature all tetrads are linked together by H-bonding patterns. 

An additional series of calculations has been carried out for the complexes of the tetrads with the metal ions. It has been concluded that the stability of such tetrads is controlled by the presence of metal ions. In this presentation, we demonstrate that such cations dominate the H-bonding patterns that govern the structures of the DNA bases polyads. 

Quantum-chemical ab initio studies have been performed on triads" " on tetrads " and on a pentad structure. Except for one recent paper we are not aware of further semiempirical calculations on base polyads. Even though semiempirical approaches 5deld occasionally sensible results we know fi om studies on nucleic acid base pairs that a consistent theoretical picture of their structure and energetics did only emerge when ab initio calculations with a consistent treatmait of electron correlation have become feasible. Hence, it is hi y recommraided to adopt non-empirical approaches for studies on base polyads. A detailed comparison of non-empirical, semiempirical and empirical approaches for the description of DNA base interactions has been performed by Hobza et al. ... 

Mismatch repair was an essential component of the Holliday model for meiotic recombination in fungi (Holliday, 1965a). This states that recombination depends on the formation of relatively short stretches of hybrid DNA between homologous chromatids within which, if they spanned a region of heterozygosity, a mispaired base-pair would appear. Mismatch repair would determine whether or not aberrant segregations would be found in the tetrads formed on completion of meiosis. 

Much like the search for protein-binding compounds requires consideration of tertiary structure in addition to peptide sequence, thinking about selective nucleic acid binding solely in the context of primary sequence is often an oversimplification. In the context of DNA recognition, a particularly important example of this is the case of G-quadruplexes. As their name implies, these structures consist of stacked tetrads of guanosine bases, typically ordered around a monovalent cation. One representative structure, a quadruplex derived from human telomeric DNA, is shown in Fig. 5 many variants of this motif formed by either parallel or antiparallel DNA strands have been observed. 

Fig. 5 Top view of a representative G-quadruplex X-ray crystal structure (human telomeric DNA PDB ID 1KF1 [7]. Guanosine bases forming tetrads are at the center of the structure in this view...

Figure 6 Example of base stacking between base pairs. Main geometric descriptors of twist and rise are shown in relation to helical axis and backbone strand polarity, (a) Duplex DNA and a GC base pair (b) a stacked tetrad consisting exclusively of guanines bases...

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