Structure of DNA

DNA is a polydeoxynucleotide and among the largest of the biological macromolecules some DNA molecules comprise more than 108 nucleotides. They contain adenine, thymine, guanine, and cytosine as the bases, and the genetic information is encoded within the nucleotide sequence, which is precisely defined over the entire length of the molecule. One of the simplest methods for determining the nucleotide sequence of DNA makes use of an enzyme, DNA polymerase, which catalyzes the synthesis of DNA. The properties of this enzyme are discussed in Chap. 16. 

The base composition of DNA from many different species has been determined. It varies from one to another (see Table 7.1). 

Question What is the base composition of DNA from human kidney  

It is the same as for human liver, as shown in Table 7.1, because the base composition of DNA is a characteristic of a particular species and does not vary from one cell type to another. This reflects the fact that the nucleotide sequence, and therefore the genetic information present, in each type of cell within an organism is exactly the same. However, as will be seen later, this information is expressed differently in the various cell types of an organism (Chap. 17). 

Are there any features common to DNA from various species with respect to the ratio of one base (or type of base) to another  

Alberts, A. B. Bray, J. Lewis, et al. Molecular Biology of the Cell. New York Garland (1994). 

Henikoff, E. A. Greene, S. Pietrokovski, et al. Gene families The taxonomy of protein paralogs and chimeras. Science 278,609 (1997). 

Ross The human genome information content and structure. Hospital Practice, June 15, 49 (1999). 

A DNA molecule is a long chain-like chemical consisting of four units called nucleotides labeled as A, C, G, and T. You may visualize it as, say, a necklace made of beads of four different colors, aquamarine (A), green (G), cobalt blue (C), and tan (T) (Fig. 4.1a). A necklace may consist of at most hundreds of beads, but a DNA molecule may be made of hundreds of thousands or even millions of these 

It turned out that the functioning DNA is a double strand. That is, it consists of two complementary strands, and this is the basis of the functions of DNA. Bead A specifically binds laterally with bead T, and G with C. Suppose that beads (a portion of a DNA) are arranged in the order of AAGCTGCAT on a strand, then on the other will be the complementary sequence TTCGACGTA, as seen in Fig. 4.1b. 

The well-known structure of a DNA is double helix (there are other types of structures known.). The double portion means donble-stranded as shown in Fig. 4.1b and is essential to the functioning of DNA. The helix portion is nonessential to the functioning of DNA, but is a result of chentical nature of the molecule and is also important in storing DNA. A DNA in the nucleus of eukaryotic cells coils up and then coils up further (supercoiled). As a result, its overall volume is reduced so that it can be confined in a small volume of nucleus. DNA cannot do this by itself. Some kinds of protein assist DNA in coiling up. 

Hydrogen bonds (...) formation between A and T (U), and between G and C Fig. 4.2 Structures of nucleotides 

Nucleotides (represented by single alphabets A, C, G, ant T) bind through the phosphate as shown in Fig. 4.3. If you combine a large number of nucleotides by this means, what you obtain is a DNA molecule (i.e., a polymer of nucleotides). You may regard the chain of (deoxy) riboses bound through phosphate as the thread (in Fig. 4.1) and the four bases as the beads in Fig. 4.1. 

The double stranded structure of DNA may also influence the site of interaction of diffusible water radicals through reduced accessibility to certain sites [19-21]. For instance, C-5 and C-6 of thymine and cytosine and C-5 and C-8 of adenine and guanine face into the major groove of DNA and are therefore solvent accessible. The distribution of radical attack at the different carbon atoms of the nucleobases may be different to that determined with the mononucleotides. In section 4.3, the influence of the accessibility of the minor groove to the hydroxyl (OH) radical on H-atom abstraction from the various carbon sites of sugar moiety is discussed. 

Complexities related to structural definitions of DNA became evident with the emergence of atomic level information. Whereas the backbone conformation of DNA has been standardized in the form of a complete set of back- 

Some of the most successful computer simulation studies of nucleic acid systems to date employ models without explicit treatment of counterions, using instead the Manning model for counterion condensation. 4 Manning developed the counterion condensation model from polyelectrolyte theories applied to DNA treated as a charged cylinder. This model, resulting from a series of studies 2,43 is summarized by  

Several other theoretical approaches, including solutions to Poisson— Boltzmann equations, quantum mechanics, and integral equation methods,have been used to characterize the electrostatics of DNA. Detailed discussion of these methods can be found in the literature and references therein. Most of these studies find that the largest electrostatic potentials for DNA are in the grooves, a property that can be useful when validating and characterizing simulation results. 

Although the results on counterion distributions in nucleic acid systems from X-ray crystallography are fragmentary, there exist several NMR studies about metals in DNA systems. - The data from NMR experiments proved to be difficult to interpret. The quadrupolar relaxation mechanism of this nuclide, originating from the electric field gradients, obfuscates the results, but in general the data are consistent with the counterion condensation theory. 

There are two types of nucleic acid—DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). We shall first consider the structure of DNA and the drugs which act on it. 

As with proteins, DNA has a primary, secondary, and tertiary structure. 

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Watson s vivid and outspoken account of how he and Crick discovered the structure of DNA (and won themselves a Nobel Prize) - one of the greatest scientific achievements of the century. 

By analogy to the levels of structure of proteins the primary structure of DNA IS the sequence of bases along the polynucleotide chain and the A DNA B DNA and Z DNA helices are varieties of secondary structures... 

We have so far described the structure of DNA as an extended double helix The crys tallographic evidence that gave rise to this picture was obtained on a sample of DNA removed from the cell that contained it Within a cell—its native state—DNA almost always adopts some shape other than an extended chain We can understand why by doing a little arithmetic Each helix of B DNA makes a complete turn every 3 4 X 10 m and there are about 10 base parrs per turn A typical human DNA contains 10 base parrs Therefore... 

A single helix is a coil a double helix is two nested coils The tertiary structure of DNA in a nucleosome is a coiled coil Coiled coils are referred to as supercoils and are quite common... 

Fig. 3. Structures of DNA alkylating/cross-linking agents given in Table 2.

Fig. 4. Structures of DNA interactive agents are given in Table 3. In structure (38) L-MeVal is 1-/V-metby1 valine.

As the molecular structure of DNA was being elucidated, scientists made significant contributions to revealing the structures of proteins and enzymes. Sanger [2] resolved the... 

Although experimental studies of DNA and RNA structure have revealed the significant structural diversity of oligonucleotides, there are limitations to these approaches. X-ray crystallographic structures are limited to relatively small DNA duplexes, and the crystal lattice can impact the three-dimensional conformation [4]. NMR-based structural studies allow for the determination of structures in solution however, the limited amount of nuclear overhauser effect (NOE) data between nonadjacent stacked basepairs makes the determination of the overall structure of DNA difficult [5]. In addition, nanotechnology-based experiments, such as the use of optical tweezers and atomic force microscopy [6], have revealed that the forces required to distort DNA are relatively small, consistent with the structural heterogeneity observed in both DNA and RNA. 

Protein folding remains a problem because there are 20 different amino acids tbat can be combined into many more different proteins tban there are atoms in the known universe. In addition there is a vast number of ways in which similar structural domains can be generated in proteins by different amino acid sequences. By contrast, the structure of DNA, made up of only four different nucleotide building blocks that occur in two pairs, is relatively simple, regular, and predictable. 

The x-ray structure of DNA complexes with 434 Cro and repressor revealed novel features of protein-DNA interactions... 

Figure 8.20 Schematic diagrams of docking the trp repressor to DNA in its inactive (a) and active (b) forms. When L-tryptophan, which is a corepressor, hinds to the repressor, the "heads" change their positions relative to the core to produce the active form of the repressor, which hinds to DNA. The structures of DNA and the trp repressor are outlined.

The breakthrough came in 1953 when James D. Watson and Francis H. C. Crick proposed a structure for DNA. The Watson-Crick proposal ranks as one of the most important in all of science and has spurred a revolution in our understanding of genetics. The structure of DNA is detailed in the next section. The boxed essay It Has Not Escaped Our Notice. .. describes how it cane about. 

In contrast, RNA occurs in multiple copies and various forms (Table 11.2). Cells contain up to eight times as much RNA as DNA. RNA has a number of important biological functions, and on this basis, RNA molecules are categorized into several major types messenger RNA, ribosomal RNA, and transfer RNA. Eukaryotic cells contain an additional type, small nuclear RNA (snRNA). With these basic definitions in mind, let s now briefly consider the chemical and structural nature of DNA and the various RNAs. Chapter 12 elaborates on methods to determine the primary structure of nucleic acids by sequencing methods and discusses the secondary and tertiary structures of DNA and RNA. Part rV, Information Transfer, includes a detailed treatment of the dynamic role of nucleic acids in the molecular biology of the cell. 

Watson, J. D., ed., 1983. Structures of DNA. Cold Spring Harbor Symposia on Quantitative Biology, Volume XLVII. New York Cold Spring Harbor Laboratory. 

The secondary biological cycles stem from the crucial roles that phosphates and particularly organophosphates play in all life processes. Thus organophosphates are incorporated into the backbone structures of DNA and RNA which regulate the reproductive processes of cells, and they... 

The first one consists of 11-12 water molecules per nucleotide unit, which are coordinated directly to sites of the DNA double helix. Two of these water molecules are bound very tightly to the ionic phosphate residue and cannot be removed without completely destroying the structure of DNA. There are four other water molecules... 

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