DNA

Deoxyribonucleic acid or DNA is a molecule which is the carrier of genetic information in nearly all the living organisms. It contains the biological instructions for the development, survival and reproduction of organisms. DNA is found in the nucleus of a cell where it is packaged into a compact form called a chromosome with the help of several proteins known as histones. It is also found in cell structures called mitochondria. However in case of prokaryotes DNA is not enclosed in a nucleus or a membrane but is present in the cytoplasm. The DNA in prokaryotes in generally circular and supercoiled without any histones. DNA stores genetic information as a sequence of nucleotides in special regions known as genes which are used to make proteins. The expression of genetic information into proteins is a two-stage process wherein the sequence of nucleotides in DNA is converted to a molecule called Ribonucleic acid or RNA by a process called transcription. RNA is used to make proteins by another process called translation. The human genome contains nearly 3 · 10⁹ bases with around 20,000 genes on 23 chromosomes. ^[1]

DNA was first discovered by the German biochemist Frederich Miescher in the year 1869.^[2] Based on the works of Erwin Chargaff, James Watson, Francis Crick, Maurice Wilkins and Rosalind Franklin, the structure of DNA was discovered in the year 1953. The structure of DNA is a double helix: two complementary strands of polynucleotides that run in opposite directions and are held together by hydrogen bonds between them.^[3] This structure helps the DNA replicate itself during cell division and also for a single strand to serve as template during transcription. ^[1]

Restore View

Features of a DNA Molecule

Double Helix

DNA consists of two polynucleotide chains, twisted around each other to form a double helix. The nucleotide in DNA is composed of a phosphate bonded to the 5' of D-2'-deoxyribose which is connected by a beta-glycosidic bond to a purine or a pyrimidine base. The ring pucker of ribose is a main determinant of which of the Forms of DNA is present. In this scene, which shows B DNA, the 2' carbon is out of the plane of the other members of the five membered ring. In A form DNA, the 3' carbon is out of the plane of the ribose ring. The four types of bases are the two double-ringed purine base Adenine (A) and Guanine (G) and the two single-ringed pyrimidine bases Thymine (T) and Cytosine (C). Hydrogen atoms on some nitrogen and oxygen atom can undergo tautomeric shifts. The nitrogen atoms that are involved in forming tautomer appear as amino or imino groups and the oxygen atoms are either in keto or enol forms. Using an isolate thymine to illustrate the imino/enol tautomer and the amino/keto tautomer. There is a preference for the amino and keto forms which is very crucial for the biological functioning of DNA as it provides a ring nitrogen capable of forming a glycosidic bond with the deoxyribose and it leads to the specificity of hydrogen bonding in base pairing and thus complementarity of the chains.^[4] The imino nitrogen can only serve as a donating atom in hydrogen bonding, but the amino nitrogen can also serve as a receiving atom. Each nucleotide in a DNA chain is linked to another via 3',5' phosphodiester bond. There are four nucleotides in DNA. The sugar-phosphate backbone of the DNA is very regular owing to the phosphodiester linkage whereas the ordering of bases is highly irregular.^[4] Restore View

A C G T

Purines Pyrimidines

Complementary Bases

The two chains in a DNA are joined by hydrogen bonds between specific bases. Adenine forms base pairs with thymine and guanine with cytosine. This specific base pairing between Adenine-Thymine and Guanine-Cytosine is known as the Watson-Crick base pairing. The specificity of hydrogen bonding between bases leads to complementarity in the sequence of nucleotides in the two chains.^[3] Thus in a strand of DNA the content of adenine is equal to that of thymine and the guanine content is equal to the cytosine content. In general DNA with higher GC content is more stable than the one with higher AT content owing to the stabilization due to base stacking interactions.

DNA denaturation and renaturation

A DNA double strand can be separated into two single strands by breaking the hydrogen bonds between them. This is known as DNA denaturation. Thermal energy provided by heating can be used to melt or denature DNA. Molecules with rich GC content are more stable and thus denature at higher temperatures compared to the ones with higher AT content. The melting temperature is defined as the temperature at which half the DNA strands are in double helical state and half are in random coil state.^[5] The denatured DNA single strands have an ability to renature and form double stranded DNA again.

Grooves

In a DNA double helix the beta-glycosyl bonds of bases which are paired do not lie opposite to each other but are positioned at an angle.

This results in unequally spaced sugar-phosphate backbones and gives rise to two grooves: the

major groove and the minor groove of different width and depth. The oxygen atoms of the furanose rings are on the surface of the minor groove, and the major groove is on the opposite side. The floor or surface of major groove is filled with the atoms of the bases. The larger size of major groove allows for the binding of DNA specific proteins.^[6][4]

Biological Functions

Sources:^[7]

Replication

DNA undergoes what is known as semi conservative mode of replication wherein the daughter DNA contains one DNA strand of the parent. The replication proceeds through the unwinding of double helix followed by synthesis primers from where the replication begins. An enzyme DNA polymerase synthesizes complementary strands to each parent strand from 5'-3' direction.

Transcription and Translation

The expression of genes into proteins and is a process involving two stages called transcription and translation. In the transcription stage a strand of DNA molecule serves as a template for the synthesis of an RNA molecule called messenger RNA. This messenger RNA is then translated into proteins on ribosomes.

Forms of DNA

For a comparison of the different forms of DNA, see forms of DNA.

History of DNA Structure

The following summary is copied from an Atlas of Macromolecules with permission:

Genes were shown to reside in DNA in 1944 (Avery et al.) and this became widely accepted after the 1952 experiments of Hershey and Chase. The double helical structure of the DNA was predicted by James Watson and Francis Crick in 1953 (Nobel Prize, 1962). Their prediction was based in part upon X-ray diffraction studies by Rosalind Franklin, to whom Watson and Maurice Wilkins gave inadequate credit^[8]. The predicted B-form double helix was not confirmed with atomic-resolution crystal structures until 1973, first by using dinucleotides of RNA (Rosenberg et al.). The first crystal structure containing more than a full turn of the double helix was not solved until 1980 (1bna, 1981, 12 base pairs). The lag of more than a quarter century between prediction and empirical confirmation involved development of X-ray crystallography for macromolecules, and the need to produce a short, defined sequence of DNA for crystallization. This brief account is based upon a review by Berman, Gelbin, and Westbrook ^[9], where the references will be found.

DNA Models

The model of DNA used in the scenes in the present article is a theoretical model^[10] (Image:B-DNA.pdb), not available in the Protein Data Bank. The PDB file does not follow certain PDB format conventions:

• Bases are designated ADE, CYT, GUA, and THY instead of the standard DA, DC, DG and DT.
• The chains are not named. Typically they would be named A and B.

One chain contains residues numbered 1-12 in sequence CGCG AATT CGCG. The other chain contains residues numbered 13-24 with an identical (antiparallel) sequence.

Theoretical models typically represent idealized DNA conformation, whereas real DNA may have various irregularities including kinks and bends (see examples bound to the Lac repressor). There are plenty of empirical models for DNA, the first having become available in the 1970's and 80's (see above). In May, 2012, the Protein Data Bank contains nearly 4,000 entries containing DNA. Over 1,300 contain only DNA, while over 2,000 contain protein-DNA complexes. Over 100 entries contain protein, DNA and RNA, and over 100 contain DNA/RNA hybrid molecules.

For more interactive visualizations of DNA, see DNA.MolviZ.Org, a tutorial that is available in nine languages.