GC base pairing

The interstrand cross-link also induces DNA bending.72 X-ray and NMR studies on this adduct show that platinum is located in the minor groove and the cytosines of the d(GC) base pair involved in interstrand cross-link formation are flipped out of the helix stack and a localized Z-form DNA is observed.83-85 This is a highly unusual structure and very distorting—implications for differential repair of the two adducts have been addressed. Alternatively, the interstrand cross-link of the antitumor inactive trans-DDP is formed between a guanine (G) and its complementary cytosine (C) on the same base p a i r.86,87/ nms- D D P is sterically incapable of producing 1,2-intrastrand adducts and this feature has been cited as a dominant structural reason for its lack of antitumor efficacy. It is clear that the structural distortions induced on the DNA are very different and likely to induce distinctly different biological consequences. 

Quinn, J.R., Ziemmerman, S.C., Del Bene, J.E. and Shavitt, I. (2007) Does the A-Tor GC base-pair possess enhanced stability Quantifying... 

A = Adenine = purine T = Thymine = pyrimidine G = Guanine = purine C = Cytosine = pyrimidine U = Uracil = pyrimidine AT/GC base pairs Antiparallel strands Major groove-minor groove A-, B-, and Z-DNA... 

The stability of the double helix is affected by the GC content. A GC base pair has three hydrogen bonds, while an AT base pair has only two. For this reason, sequences of DNA that are GC-rich form more stable structures than AT-rich regions. 

AT/GC base pairs Antiparallel strands Major groove-minor groove A-, B-, and Z-DNA... 

How strong the overall GC content of an siRNA influences its activity remains controversial in the literature. While some studies claim that the optimal GC content of an siRNA is 30-50%, others have found that also GC-rich siRNAs with GC contents of about 60% are highly efficient (35, 36). We therefore recommend using siRNAs with an overall GC content between 30 and 65% of base pairing nucleotides. It has been shown that GC stretches of 9 or more nucleotides anywhere in the base pairing sequence of an siRNA reduce its efficiency. In addition, siRNAs with low GC content (not more than two GC base pairs) in the 5 terminal third of the guide (antisense) strand are likely to be potent siRNAs (36). Therefore these two parameters should be taken into account when designing siRNAs. 

Figure 1 Free radical structures, parent compounds, and stable end products for the various components of DNA (a) deoxyribose, (b) guanine, (c) adenine, (d) thymine, and (e) cytosine. Panel (f) shows trapping of the electron and hole by proton transfer in the GC base pair in duplex DNA.

FIGURE 4. Typical outer-sphere interaction of [Mg(H20)5] with two GC base pairs in the major groove of a DNA double helix... 

Here AB is the difference in ionization potentials of AT and GC base pairs, b is the transfer integral, c, and c, are the creation and annihilation operators for a hole at the f-th site, respectively, index i labels DNA base pairs in the sequence, and the sum E is taken over GC sites only. 

In the case of DNA, Troisi and Orlandi [26] have completed an integrated molecular dynamics/electronic structure study that examines precisely the issue of the dependence of the matrix element on geometry. These investigators studied a ten-base-pair double helical strand, whose interior contained two GC base pairs separated by four AT base pairs. They placed... 

The Porath et al. experiment [14], reviewed in Sect. 2, reports nonlinear transport measurements on 10.4-nm-long poly(dG)-poly(dC) DNA, corresponding to 30 consecutive GC base pairs, suspended between platinum leads (GC-device). DFT calculations indicated that the poly(dG)-poly(dC) DNA molecule has typical electronic features of a periodic chain [58]. Thus, in both models (assuming dephasing or r-stack hybridization) the poly(dG)-poly(dC) DNA molecule is grained into a spinless linear TB chain. A generalization of the dephasing model to spin-transport has been proposed by Zwolak et al. [123]. 

Fig. 22 Schematic view (left) of a fragment of poly(dG)-poly(dC) DNA molecule each GC base pair is attached to sugar and phosphate groups forming the molecule backbone. On the right side, the diagram of the lattice adopted in building our model, with the r-stack connected to the isolated states denoted as -edges. The total Hamiltonian...

Fic. 5.A7. AT and GC base pairs held together by hydrogen bonding... 

Dornberger U, Leijon M, Fritzsche H (1999) High base opening rates in tracks of GC base pairs. J Biol Chem 274 6957-6962... 

According to Equation 6.2 and typical cellular conditions, what is the Tm of a duplex strand of DNA as the length approaches infinity (The ratio of GC base pairs to AT in the human genome is approximately 40 60.)... 

Transcription continues until a termination sequence is reached. The most common termination signal is a GC-rich region that is a palindrome, followed by an AT-rich sequence. The RNA made from the DNA palindrome is self-complementary and so base-pairs internally to form a hairpin structure rich in GC base pairs followed by four or more U residues (Fig. 4). However, not all termination sites have this hairpin structure. Those that lack such a structure require an additional protein, called rho (p), to help recognize the termination site and stop transcription. 

Most groove binders have binding selectivity toward AT-rich areas, because grooves, which consist of GC base pairs, are sterically hindered by the guanine amino functionality at C-2 and its hydrogen bond with the C-2 carbonyl functionality of... 

The sugar phosphate backbone is on the outside, and the bases point inward. These bases are paired so that for each adenine (A) on one chain a thymine (T) is aligned opposite it on the other chain. Each cytosine (C) on one chain has a guanine (G) aligned with it on the other chain. The AT and GC base pairs form hydrogen bonds with each other. The AT pair has two hydrogen bonds the GC pair has three hydrogen bonds (Fig. 47.1). 

Show the GC base pair structure before and after the addition of an acid. 

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