DNA STRUCTURE & FUNCTION

CONTENTS Page
The Discovery of DNA:3
Components of DNA:5
Purine Bases:5
Pyrimidine Bases:6
Deoxyribose Sugar:6
Nucleosides:7
Nucleotides:7
DNA Backbones:8
DNA Double Helix:8
Base Pairs :9
DNA Helix Axis:11



The Discovery of DNA
In 1953 James D. Watson and Francis H.C. Crick published a paper in which they proposed a model for the physical and chemical structure of the DNA molecule. According to their model, most DNA consists of two polynucleotide chains wound around each other in a right-handed (clockwise) helix. In generating their model, Watson and Crick used three main pieces of evidence:
1. The DNA molecule was known to be composed of bases, sugars, and phosphate groups linked together as a polynucleotide (deoxyribonucleotide) chain.
2. By chemical treatment Erwin Chargaff had hydrolyzed the DNA of a number of organisms and had quantified the purines and pyrimidines released. His studies showed that in all the (double-stranded) DNAs the amount of the purines was equal to the amount of the pyrimidines. More important, the amount of adenine (A) was equal to the amount of thymine (T), and the amount of guanine (G) was equal to that of cytosine (C). These equivalencies have become known as Chargaff's rules. In comparisons of DNAs from different organisms, the A/T and G/C ratios are always the same, although the (A+T)/(G+C) ratio (typically presented as %GC) varies.
3. Rosalind Franklin, working with Maurice H.F. Wilkins, studied isolated fibers of DNA by using the X-ray diffraction technique, a procedure in which a beam of parallel X rays is directed on a regular, repeating array of atoms. The beam is diffracted by the atoms in a pattern that is characteristic of the atomic weight and the spatial arrangement of the molecules. The diffracted X rays are recorded on a photographic plate. By analyzing the photograph, Franklin could obtain information about the molecule's atomic structure. The analysis of X-ray diffraction patterns is extremely complicated. As a result, given diffraction patterns can usually be interpreted in more than one way, and models built of the analyzed molecules may not be accurate. Moreover, since the experiments usually use molecules in a crystalline or fiber formation, the structures deduced may not precisely reflect the form of the molecules in the cell.
The diffraction patterns obtained by directing X-rays along the length of drawn-out fibers of DNA indicated that the molecule is organized in a highly ordered, helical structure. Franklin interpreted these kinds of data to mean that DNA was a helical structure which had two distinctive regularities of 0.34 nm and 3.4 nm along the axis of the molecule. Watson and Crick considered all the evidence just described and began to build three-dimensional models for the structure of DNA. The model they devised, which fit all the known data on the composition of the DNA molecule, is the now-famous double-helix model for DNA. Unquestionably, the determination of the structure of DNA was a momentous occasion in biology, leading directly to many Nobel prize-winning discoveries in molecular biology. The double-helical model of DNA proposed by Watson and Crick has the following main features:
1. The DNA molecule consists of two polynucleotide chains wound around each other in a right-handed double helix; that is, viewed on end, the two strands wind around each other in a clockwise (right-handed) fashion.
2. The diameter of the helix is 2 nm.
3. The two chains are antiparallel(= show opposite polarity); that is, the two strands are oriented in opposite directions with one strand oriented in the 5' to 3' way, while the other strand is oriented 3' to 5'.
4. The sugar-phosphate backbones are on the outsides of the double helix, while the bases are oriented toward the central axis. The bases of both chains are flat structures oriented perpendicularly to the long axis of the DNA; that is, the bases are stacked like pennies on top of one another (except for the "twist" of the helix).
5. The bases of the opposite strands are bonded together by relatively weak hydrogen bonds. The only specific pairings are A with T (two hydrogen bonds) and G with C (three hydrogen bonds). The weak hydrogen bonds make it relatively easy to separate the two strands of the DNA, for example, by heating. Breaking the A-T base pair by heating is easier than breaking the G-C base pair because A-T has two hydrogen bonds and G-C has three hydrogen bonds. The A-T and G-C base pairs are the only ones that can fit the physical dimensions of the helical model, and they are totally in accord with Chargaff's rules. The specific A-T and G-C pairs are called complementary base pairs, so the nucleotide sequence in one strand dictates the nucleotide sequence of the other.
6.The base pairs are 0.34 nm apart in the DNA helix. A complete (360 degrees) turn of the helix takes 3.4 nm; therefore, there are 10 base pairs per turn. Each base pair, then, is twisted 36 degrees clockwise with respect to the previous pair.
7. Because of the way the bases bond with each other, the two sugar-phosphate backbones of the double helix are not equally spaced along the helical axis. This results in grooves of unequal size between the backbones called the major groove (the wider groove of the two) and the minor groove (the narrower groove of the two). Both of these grooves are large enough to allow protein molecules to make contact with the bases. The phenomenon of proteins "reading" specific base-pair sequences is common to many molecular processes.


Components of DNA
DNA is a polymer. The monomer units of DNA are nucleotides, and the polymer is known as a "polynucleotide." Each nucleotide consists of a 5-carbon sugar (deoxyribose), a nitrogen containing base attached to the sugar, and a phosphate group. There are four different types of nucleotides found in DNA, differing only in the nitrogenous base. The four nucleotides are given one letter abbreviations as shorthand for the four bases.
• A is for adenine
• G is for guanine
• C is for cytosine
• T is for thymine
Purine Bases
Adenine and guanine are purines. Purines are the larger of the two types of bases found in DNA. Structures are shown below:
Structure of A and G

The 9 atoms that make up the fused rings (5 carbon, 4 nitrogen) are numbered 1-9. All ring atoms lie in the same plane.
Pyrimidine Bases
Cytosine and thymine are pyrimidines. The 6 stoms (4 carbon, 2 nitrogen) are numbered 1-6. Like purines, all pyrimidine ring atoms lie in the same plane.
Structure of C and T


Deoxyribose Sugar
The deoxyribose sugar of the DNA backbone has 5 carbons and 3 oxygens. The carbon atoms are numbered 1', 2', 3', 4', and 5' to distinguish from the numbering of the atoms of the purine and pyrmidine rings. The hydroxyl groups on the 5'- and 3'- carbons link to the phosphate groups to form the DNA backbone. Deoxyribose lacks an hydroxyl group at the 2'-position when compared to ribose, the sugar component of RNA.
Structure of deoxyribose

Nucleosides
A nucleoside is one of the four DNA bases covalently attached to the C1' position of a sugar. The sugar in deoxynucleosides is 2'-deoxyribose. The sugar in ribonucleosides is ribose. Nucleosides differ from nucleotides in that they lack phosphate groups. The four different nucleosides of DNA are deoxyadenosine (dA), deoxyguanosine (dG), deoxycytosine (dC), and (deoxy)thymidine (dT, or T).
Structure of dA


In dA and dG, there is an "N-glycoside" bond between the sugar C1' and N9 of the purine.
Nucleotides
A nucleotide is a nucleoside with one or more phosphate groups covalently attached to the 3'- and/or 5'-hydroxyl group(s).

DNA Backbone
The DNA backbone is a polymer with an alternating sugar-phosphate sequence. The deoxyribose sugars are joined at both the 3'-hydroxyl and 5'-hydroxyl groups to phosphate groups in ester links, also known as "phosphodiester" bonds.

Example of DNA Backbone: 5'-d(CGAAT):


Features of the 5'-d(CGAAT) structure:
• Alternating backbone of deoxyribose and phosphodiester groups
• Chain has a direction (known as polarity), 5'- to 3'- from top to bottom
• Oxygens (red atoms) of phosphates are polar and negatively charged
• A, G, C, and T bases can extend away from chain, and stack atop each other
• Bases are hydrophobic


DNA Double Helix
DNA is a normally double stranded macromolecule. Two polynucleotide chains, held together by weak thermodynamic forces, form a DNA molecule.

Structure of DNA Double Helix

Features of the DNA Double Helix
• Two DNA strands form a helical spiral, winding around a helix axis in a right-handed spiral
• The two polynucleotide chains run in opposite directions
• The sugar-phosphate backbones of the two DNA strands wind around the helix axis like the railing of a sprial staircase
• The bases of the individual nucleotides are on the inside of the helix, stacked on top of each other like the steps of a spiral staircase.


Base Pairs
Within the DNA double helix, A forms 2 hydrogen bonds with T on the opposite strand, and G forms 3 hyrdorgen bonds with C on the opposite strand.
• dA-dT and dG-dC base pairs are the same length, and occupy the same space within a DNA double helix. Therefore the DNA molecule has a uniform diameter.
• dA-dT and dG-dC base pairs can occur in any order within DNA molecules
Example of dA-dT base pair as found within DNA double helix
Example of dG-dC base pair as found within DNA double helix
DNA Helix Axis
The helix axis is most apparent from a view directly down the axis. The sugar-phosphate backbone is on the outside of the helix where the polar phosphate groups (red and yellow atoms) can interact with the polar environment. The nitrogen (blue atoms) containing bases are inside, stacking perpendicular to the helix axis.
View down the helix axis