The Structure of DNA

Representations of the double-helical structure of DNA have become common in the popular press as well as in the scientific literature. When the double helix was proposed by James Watson and Francis Crick in 1953, it touched off a flood of research activity, leading to great advances in molecular biology. 

The X-ray diffraction pattern of DNA demonstrated the helical structure and the diameter. The combination of evidence from X-ray diffraction and chemical analysis led to the conclusion that the base pairing is complementary, meaning that adenine pairs with thymine and that guanine pairs with cytosine. Because complementary base pairing occurs along the entire double helix, the two chains are also referred to as complementary strands. By 1953, studies of the base composition of DNA from many species had already shown that, to within experimental 

Chapter 9 Nucleic Acids How Structure Conveys Information 

Are there other possible conformations of the double helix  

The form of DNA that we have been discussing so far is called B-DNA. It is thought to be the principal form that occurs in nature. However, other secondary 

The individual DNA molcule which localized in eukaryotic chromosomes are large polymers and they contain a linear backbone of alternating sugar and phosphate residues. DNA molecule includes the five carbon sugar deoxyribose, and consecutive sugar structures are linked by covalent phosphodiester bridge. Covalently bonded to carbon atom number V (one prime) of each sugar is a 

While covalent bonds don t get affected from heat, noncovalent bonds can be broken reversibly by a high temperature. For molecular interactions in living cells, this situation is desired because it plays an essential role in biological functioning. This reversible interactions are also used in the development of bisensor systems. 

Most of the DNAs have a B-DNA in living cells. DNAs also have different helical structures such as A-DNA or Z-DNA. A and B forms of DNAs are both right-handed helices (clockwise direction) and their one turns contains 11 (A form) and 10 (B form) base pairs. Left-handed Z-DNA form has 12 base pairs per turn. 

The distance between turns of the helix is called a pitch which is 3.4 nm long. 

1 pitch (3.4 nm) = minor groove length + major groove length The double-stranded DNA molecule also has an antiparallel nature because the two strands have opposite directions for the linking of a 3 carbon atom with a 5 carbon atom. According to 

---

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. 

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... 

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. 

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. 

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... 

James Dewey Watson (1928- ) was born in Chicago, Illinois, and enrolled in the University of Chicago at age 15. He received his Ph.D. in 1950 at the Unwersity of Indiana and then worked at Cambridge University in England from 1951 to 1953, where he and Francis Crick deduced the structure of DNA. After more than 20 years as professor at Harvard University, he moved in 1976 to the Laboratory of Quantitative Biology at Cold Spring Harbor, Long Island, New York. He shared the 1962 Nobel Prize in medicine for his work on nucleic acids. 

Double helix (Section 28.2) The structure of DNA in which two polynucleotide strands coil around each other. 

The antimetabolites interfere with various metabolic functions of cells, thereby disrupting normal cell functions. They inactivate enzymes or alter the structure of DNA, changing the DNA s ability to replicate These drag are most effective in the treatment of rapidly dividing neoplastic cells. Examples of the antimetabolites include methotrexate and fluorouracil (Adrucil). 

You might learn about the structure of DNA at the end of your organic chemistry course. For right now, we will be focused on problems that deal primarily with small molecules and therefore, for our purposes, we should think of H-bonding as an interaction a type of intermolecular force. 

Phosphoric acid or phosphate can also condense with an alcohol to generate a phosphate linkage. As described later, such linkages are found in the structure of DNA. 

By now the stage was set for the discoveiy of the three-dimensional structure of DNA, the so-called secondary structure of the molecule. Some of the best minds in science were working on the problem. In 1953, James D. Watson and Francis Crick of Cambridge University announced that they had discovered the structure of DNA. 

The structure of DNA was discovered by (shown left to right) Francis Crick, James Watson, Maurice Wilson, and Rosalind Franklin. 

The structure of DNA. (a) A ball-and-stick model, with the sugar-phosphate backbone colored blue and the bases colored red. b) A space-filling model, showing C atoms in blue, N atoms in dark blue, H atoms in white, O atoms in red, and P atoms in yellow. 

In recent years, our detailed understanding of the structure of DNA and how it functions has led to many new methods of genetic manipulation. Our Box explores one aspect of this subject. 

The structures of DNA and RNA are similar in that each has a sugar-phosphate backbone with one organic base bound to each sugar. However, there are four distinct differences between RNA and DNA ... 

The structure of DNA resembles a ladder that has been twisted around itself. The rungs of the ladder are composed of bases (guanine, thymine, cytosine, and adenine) that form hydrogen bonds. 

In 1953, James Watson and Francis Crick determined that the structure of DNA was a double helix. This discovery best helped them —... 

It is now almost 50 years since the structure of DNA was elucidated by Watson and Crick (1) (Fig. 1). Since then the double helix has become an icon for modern scientific achievement. With the rapid growth of molecular biology and the consequent success of the human genome project (2) we are now firmly in a post-genomic era. However, in spite of, or perhaps because of this, efforts to understand fundamental aspects of metal-ion interactions with DNA continue to be vigorously pursued. 

Implicit in the functioning of the Watson-Crick DNA model is the idea that the strands of a DNA molecule must separate and new daughter strands must be synthesized in response to the sequence of bases in the mother strand. This is called semiconservative replication. Still, conservative replication, in which both strands of a daughter molecule are newly synthesized, could not be ruled out by consideration of the structure of DNA alone. 

Then came the year 1953, and with it important events, both political and scientific in nature the death of Stalin and the determination of the structure of DNA in addition, a scientific article was published in Science by a previously unknown author, Stanley L. Miller. Its title was A Production of Amino Acids under Possible Primitive Earth Conditions (Miller, 1953). 

The mechanism of carcinogenesis by PAHs is believed to involve alkylation of an informational macromolecule in a critical, but at present unknown, manner. Such an interaction with a protein has been modelled by alkylation of a peptide this showed a conformational change occurred on alkylation. It has not yet been possible to study the structure of DNA alkylated by an activated carcinogen this is because DNA is a fiber and the structural order in it is not sufficient for a crystal structure determination. However the crystal structures of some alkylated portions of nucleic acids are described, particularly some nucleosides alkylated by chloromethyl derivatives of DMBA. In crystals of these alkylation products the PAH portion of the adduct shows a tendency to lie between the bases of other nucleoside... 

Much of what we know about the regulation of information flow (gene expression) has been made possible by the ability to manipulate the structures of DNA, RNA, and proteins and see how this affects their function. The ability to manipulate DNA (recombinant-DNA methods) has generated a new language filled with strange-sounding acronyms that are easy to understand if you know what they mean but impossible to understand if you don t. Understand ... 

Johnson RR, Johnson ATC, Klein ML (2008) Probing the Structure of DNA-Carbon Nanotube Hybrids with Molecular Dynamics. Nano Lett. 8 69-75. 

Watson and Crick s discovery of the structure of DNA revolutionized scientists understanding of heredity and genetics. Find out how Watson and Crick showed that the structure of DNA is a double helix. How did Rosalind Franklin s work in X-ray crystallography play a role Present your findings as an annotated, illustrated time line. 

---