DNA Structure and Functions (a quick Revision)

DNA

• DNA – a polymer of deoxyribonucleotides
• found in chromosomes, mitochondria, and chloroplasts
• carries the genetic information.

DNA structure

a) Primary structure (figure-1)

• Represents the linear sequence of deoxyribonucleotides linked together by 3′-5′ phosphodiester linkages
• The informational content of DNA resides in the sequence in which monomers—purine and pyrimidine deoxyribonucleotides—are ordered
• The polymer as depicted possesses a polarity; one end has a 5′-hydroxyl or phosphate terminal while the other has a 3′-phosphate or hydroxyl terminal.
• Traditionally, a DNA sequence is drawn from 5’ to 3’ end.

Figure-1- showing the structure of a linear single-stranded DNA fragment, individual nucleotides are linked together by 3′-5’phosphodiester linkage. DNA strand has a polarity (5′ Free end and a 3′ free or unattached end). In a single-stranded DNA, the sequence is written in the 5′ to 3′ direction.

b) Secondary structure (Figure- 2)

The secondary structure of DNA is the double-helical structure as proposed by Watson, Crick, and Wilkins

• The two strands of the double-helical molecule, each of which possesses a polarity, are antiparallel; ie, one strand runs in the 5′ to 3′ direction and the other in the 3′ to 5′ direction.
• Sugar-phosphate chains wrap around the periphery.
• Bases (A, T, C, and G) occupy the core, forming complementary A · T and G · C Watson-Crick base pairs.
• The DNA double helix is held together mainly by- Hydrogen bonds.
• Two hydrogen bonds between A: T pairs while three hydrogen bonds between C: G pairs
• The bases in DNA are planar and have a tendency to “stack”.
• Major stacking forces: hydrophobic interaction and Vander Waals forces.
• This common form of DNA is said to be right-handed because as one looks down the double helix, the base residues form a spiral in a clockwise direction.
• In a double-helical structure, Chargaff rule is followed which states that in DNA molecules the concentration of deoxyadenosine (A) nucleotides equals that of thymidine (T) nucleotides (A = T), while the concentration of deoxyguanosine (G) nucleotides equals that of deoxycytidine (C) nucleotides (G = C).
• In the double-stranded DNA molecules, the genetic information resides in the sequence of nucleotides on one strand, the template strand. This is the strand of DNA that is copied during ribonucleic acid (RNA) synthesis. It is sometimes referred to as the noncoding strand. The opposite strand is considered the coding strand because it matches the sequence of the RNA transcript (but containing uracil in place of thymine) that encodes the protein.
• There are Grooves in the DNA Molecule- a major groove and a minor groove winding along the molecule parallel to the phosphodiester backbones. In these grooves, proteins can interact specifically with exposed atoms of the nucleotides (via specific hydrophobic and ionic interactions) thereby recognizing and binding to specific nucleotide sequences without disrupting the base pairing of the double-helical DNA molecule.
• Double-stranded DNA exists in at least six forms (A–E and Z). The B form is usually found under physiologic conditions (low salt, a high degree of hydration).
• A single turn of B-DNA about the axis of the molecule contains ten base pairs. The distance spanned by one turn of B-DNA is 3.4 nm (34 Å). The width (helical diameter) of the double helix in B-DNA is 2 nm (20 Å).

 

Figure-2-  showing a  diagrammatic representation of the Watson and Crick model of the double-helical structure of the B form of DNA. The horizontal arrow indicates the width of the double helix (20 Å), and the vertical arrow indicates the distance spanned by one complete turn of the double helix (34 Å). The major and minor grooves are depicted. Hydrogen bonds between A/T and G/C bases indicated by short horizontal lines.

 Structural forms of DNA

Property	A-DNA	B-DNA	Z-DNA
Helix Handedness	Right	Right	Left
Base Pairs per turn	11	10.4	12
Rise per base pair along axis	0.23 nm	0.34 nm	0.38 nm
Pitch	2.46 nm	3.40 nm	4.56 nm
Diameter	2.55 nm	2.37 nm	1.84 nm
Conformation of Glycosidic bond	anti	anti	Alternating anti and syn
Major Groove	Present	Present	Absent
Minor Groove	Present	Present	Deep cleft

c) Tertiary structure-In eukaryotic cells,  DNA is folded into chromatin. Chromatin consists of very long double-stranded DNA molecules and a nearly equal mass of rather small basic proteins termed histones as well as a smaller amount of nonhistone proteins (most of which are acidic and larger than histones) and a small quantity of the double-stranded DNA helix in each chromosome has a length that is thousands of times the diameter of the cell nucleus. One purpose of the molecules that comprise chromatin, particularly the histones, is to condense the DNA.

Levels of organization of DNA (figure-3)

• Nucleosomes are composed of DNA wound around a collection of histone molecules.
• The disk-like nucleosome structure has a 10-nm diameter and a height of 5 nm. The 10-nm fibril consists of nucleosomes arranged with their edges separated by a small distance (30 bp of DNA) with their flat faces parallel with the fibril axis.
• The 10-nm fibril is probably further supercoiled with six or seven nucleosomes per turn to form the 30-nm chromatin fiber.
• In interphase chromosomes, chromatin fibers appear to be organized into 30,000–100,000 bp loops or domains anchored in a scaffolding (or supporting matrix) within the nucleus.
• At metaphase, mammalian chromosomes possess a twofold symmetry, with the identical duplicated sister chromatids connected at a centromere, the relative position of which is characteristic for a given chromosome (Figure-3)

Figure-3- showing the different levels of organization of DNA structure.

Functions of DNA

The genetic information stored in the nucleotide sequence of DNA serves two purposes.

• It is the source of information for the synthesis of all protein molecules of the cell and organism,
• it provides the information inherited by daughter cells or offspring.
• Both of these functions require that the DNA molecule serves as a template—in the first case for the transcription of the information into RNA and in the second case for the replication of the information into daughter DNA molecules.