A-T pairs

As indicated in Chapter 11, the base pairing in DNA is very specific the purine adenine pairs with the pyrimidine thymine the purine guanine pairs with the pyrimidine cytosine. Further, the A T pair and G C pair have virtually identical dimensions (Figure 12.10). Watson and Crick realized that units of such similarity could serve as spatially invariant substructures to build a polymer whose exterior dimensions would be uniform along its length, regardless of the sequence of bases. 

FIGURE 12.18 The dependence of melting temperature on relative (G + C) content in DNA. Note that T increases if ionic strength is raised at constant pH (pH 7) 0.01 M phos-phate+0.001 MEDTA versus 0.15 M NaCl/0.015 MNa citrate. In 0.15 M NaCl/0.015 MNa citrate, duplex DNA consisting of 100% A T pairs melts at less than 70 C, whereas DNA of 100% G C has a T greater than 110 "C. (From Marmur Jo and Doty, R, 1962. Journal of Molecular Biology 5 120.)... 

Methods of data analysis for reactions in solids are somewhat different from those used in other types of kinetic studies. Therefore, the analysis of data for an Avrami type rate law will be illustrated by an numerical example. The data to be used are shown in Table 8.1, and they consist of (a,t) pairs that were calculated assuming the A3 rate law and k = 0.025 min-1. 

Cytosine can become deaminated spontaneously or by reaction with nitrous acid to form uracil. This leaves an improper base pair (G-U), which is eliminated by a base excision repair mechanism (Figure 1-2-5). Failure to repair the improper base pair can convert a normal G-C pair to an A-T pair. 

Salganik, Drefich, and Vasgunina173 report that the denatured regions of DNA irradiated with ultraviolet light are the regions rich in A-T pairs, and that these regions contain most of the thymine dimers. 

Native DNA undergoes reversible unwinding and separation of strands (melting) on heating or at extremes of pH DNAs rich in G C pairs have higher melting points than DNAs rich in A=T pairs. 

The centromere (Fig. 24-9) is a sequence of DNA that functions during cell division as an attachment point for proteins that link the chromosome to the mitotic spindle. This attachment is essential for the equal and orderly distribution of chromosome sets to daughter cells. The centromeres of Saccharomyces cere-visiae have been isolated and studied. The sequences essential to centromere function are about 130 bp long and are very rich in A=T pairs. The centromeric sequences of higher eukaryotes are much longer and, unlike those of yeast, generally contain simple-sequence DNA, which consists of thousands of tandem copies of one or a few short sequences of 5 to 10 bp, in the same orientation. The precise role of simple-sequence DNA in centromere function is not yet understood. 

For example, Hoogsteen proposed an alternative A-T pairing using the 6-NH2 and N-7 of adenine.34 Here the distance spanned by the base pair, between the C-T sugar carbons, is 0.88 nm, less than the 1.08 ran of the Watson-Crick pairs. Duplexes of certain substituted poly (A) and poly (U) chains contain only Hoogsteen base pairs35 and numerous X-ray structure determinations have established that Hoogsteen pairs... 

At this point, it may be interesting to indicate that the fact that the G-C pairs constitute the unstable part of the genome and that they mutate spontaneously more frequently than the A-T pairs has been reported in a number of publications.180-182 One cannot and should not, however, conclude from this situation that miscouplings through tautomerization of bases are the principal cause of spontaneous mutations, because those are definitely known to be due to a large series of causes, the relative importance of which is difficult to ascertain. The concordance between the theoretical predictions and the experimental facts is, however, worthwhile stressing, as an eventual discordance would certainly have been by some. 

Table XX confirms, as indicated in Section I of this review, that among the natural complementary pairs, the G-C pair has a much greater interaction energy than the A-T pair. It shows also that...

Sources of deoxyuridine in DNA include the presence of dUTP because dUMP (the substrate for thymidylate synthase) or dUDP (from ribonucleotide reductase action on UDP) are phosphorylated to the triphosphate. DNA polymerase recognizes these compounds as substrates. Another source is the deamination of deoxycytidine in DNA, promoted by a variety of compounds. If deoxyuridine is on a template strand of the DNA, it will direct the incorporation of an A in the newly made strand of DNA. This will convert a G-C pair to an A-T pair. 

Ribose and deoxyribose contribute to the formation of RNA and DNA, respectively. Binding of a base to the pentose yields a nucleoside, and binding of a phosphoric acid to the nucleoside forms a nucleotide. Finally, different nucleotides bound together form a nucleic acid. There is a specific complementary nature to the bases adenine with thymine and guanine with cytosine. The C-G pair has three hydrogen bonds, while the A-T pair has only two, thus preventing incorrect pairing. The sequence of the bases determines the primary structure of the DNA. 

DNA is a duplex molecule in which two polynucleotide chains (or strands) are linked to one another through specific base pairing (Fig. 7-1). Adenine in one strand is paired to thymine in the other, and guanine is paired to cytosine. The two chains are said to be complementary. This was one of the essential features of Watson and Crick s proposal regarding the structure of DNA. Hydrogen bonds form between the opposing bases within a pair. In the structure proposed by Watson and Crick, A T and G C base pairs are roughly planar, with H bonds (dotted lines), as shown in Fig. 7-1. Note that two H bonds form in an A T pair and three in a G C pair. 

By using synthetic duplex DNA molecules in which every hopping step between adjacent G-C pairs involves the same number (two) of intervening A-T pairs, the validity of equation (8), with 77 = 1.7 was demonstrated.160... 

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