DNA consists of two strands, that wind around each other. Each strand has repeating units of a nitrogenous base, deoxyribose sugar, and a phosphate group. There are several interactions present within a strand and between two strands that stabilize the DNA.
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Covalent Bonds (intrastrand bonds)
Each strand consists of the following:
- Base (Adenine, Thymine, Guanine, Cytosine)
- Deoxyribose sugar
- Phosphate group
There are four bases: Adenine and Guanine (purines); Cytosine and Thymine (Pyrimidines). Purines have two carbon-nitrogen rings while pyrimidines have a single carbon-nitrogen ring. Thus, there are four different nucleotides that can be incorporated into DNA.
Based on which base is attached, the nucleotides are called 2’-deoxyadenosine triphosphate, 2’-deoxycytidine triphosphate, 2’-deoxyguanosine triphosphate, or 2’-deoxythymidine triphosphate. Each of these bases is connected to 1’-carbon of the deoxyribose sugar.
In an unattached and free nucleotide, there is a triphosphate group on the 5’-carbon of the deoxyribose sugar. However, when a nucleotide is incorporated into a DNA strand, it loses two of the phosphate groups and only one phosphate group is added to the DNA strand.
This addition involves formation of a covalent bond called the ‘phosphodiester bond’. This is formed between the 5’-phosphate group of one nucleotide and the 3’-OH group of another nucleotide forming a sugar-phosphate backbone of DNA.
The hydrogen bonds between the base pairs form the double helical structure of DNA. There is no exchange or sharing of electrons in hydrogen bonds as seen in covalent or ionic bonds. Hydrogen bonds occur over short distances and can be easily formed and broken. Although individually each hydrogen bond is much weaker than the covalent bond, they can stabilize the double helix because of their large numbers.
This pairing is very specific: adenine pairs with thymine and cytosine pairs with guanine. This selective pairing is called ‘complementary base pairing’. A-T pair forms two hydrogen bonds, while C-G pair forms three. The sugar-phosphate chains form the backbone of the ladder-like DNA structure and these base pairs form the rungs. The width of each of these ‘rungs’ are the same as it involves one purine (A or G) and one pyrimidine (C or T) base.
a) Hydrophobic effects
DNA has an interesting arrangement wherein the non-polar, uncharged bases are present in the interior of the structure, while the negatively charged phosphates are present on the outside. As the cellular environment is aqueous and polar, the hydrophobic bases in the interior of the helix are kept away from the surrounding water and the hydrophilic heads are exposed and interact with the exterior water. This property increases the solubility of DNA in water.
b) Van der Waals forces
The nitrogenous bases stacked upon one another are spaced based on their van der Waals distance. Van der Waals distance is the distance at which two molecules are attracted to each other. If this distance reduces, the electrons of the two molecules may overlap causing repulsion. These forces are very distance dependent and are inversely proportional to the sixth power of distance (r6 ). Although a single van der Waals interaction has a very small effect on the overall structure of DNA, the net effect of several interactions lead to substantial stability.
c) Ionic interactions
The electrostatic (ion-ion) repulsion of the negatively charged phosphates on the outside can make DNA potentially very unstable. However, magnesium ions (Mg2+) and cationic proteins along with arginine and lysine residues interact with the negatively charged groups in the DNA and stabilize it.
The strength and stability of DNA stacking interactions has been scientifically proved by demonstrating that the use of compounds (urea, formamide) that interfere with hydrogen bonds do not separate the strands completely, suggesting the presence of additional forces at work.
Reviewed by Deepthi Sathyajith, MPharm