Deoxyribonucleic acid (DNA) is the material of which genes are made. This had not been widely accepted until 1953 when J.D. Watson and F.H, Crick proposed a structure for DNA which accounted for its ability to self- replicate and to direct the synthesis of proteins. All living cells (both prokaryotic and eukaryotic) contain double stranded DNA as their genetic material. DNA is composed of a series of polymerized nucleotides, joined by phosphodiester bonds between the 5' and 3' carbons of deoxyribose units. DNA forms a double helix with these strands, running in opposite orientations with respect to the 3' and 5' hydrozxy groups. The double helix structure is stabilized by base pairing between the nucleotides, with adenine and thymine forming two hydrogen bonds, and cytosine and guanine forming three. Base + Sugar = nucleoside Base + Sugar + Phosphate Group = nucleotide Attached to each sugar residue is one of the four essentially planar nitrogenic organic bases: Adenine A, Cytosine C, Guanine G, Thymine T, The plane of each base is essentially perpendicular to the helix axis. Encoded in the order of the bases along a strand is the hereditary information. The two strands coil about each other so that all the bases project inward towards the helix axis. The two strands are held together by hydrogen bonds linking each base projecting from one backbone to its complementary base projecting from another backbone. The base A always binds to T and C always binds to G. This complementary pairing allows DNA to serve as a template for its own replication. Linking any two sugar residues is an -O--P--O-, a phosphate bridge between the 3' carbon atom of one of the sugars and the 5' carbon atom of the other sugar. Note that in solution DNA is negatively charged due to the presence of the phosphate group. Because deoxyribose has an asymmetric structure, the ends of each strand of a DNA fragment are different. At one end the terminal carbon atom in the backbone is the 5' carbon atom of the terminal sugar (the carbon atom that lies outside the planar portion of the sugar); and at the other end it is the 3' carbon atom (one that lies within the planar portion of the sugar). Double helical DNA in cells is an exceptionally long and stiff polymer. The winding and unwinding of the double helix for replication and transcription in the constrained intracellular space available to it, makes for the topological and energetic problems of DNA Supercoiling. DNA in a circular form is often supercoiled. Negatively supercoiled DNA is in a more compact shape than relaxed DNA and is partially unwound, facilitating interactions with enzymes such as polymerases. Positive supercoiling results in the same space conservation as negative supercoiling, but makes DNA harder to work with. Negative supercoiling facilitates the separation of strands for replication, recombination, and transcription, and is therefore the preferred form for most natural DNA molecules. Two enzymes work to maintain supercoiling in DNA: 1) Topoisomerases relax supercoiled DNA, and 2) DNA gyrase introduces supercoiling.