ESSENTIAL MOLECULAR
BIOLOGY
,L1: DNA STRUCTURE AND FUNCTION
DNA DOUBLE HELIX STRUCTURE
- Watson and Crick deducted DNA structure (1953)
- Information came from Franklin via X-ray diffraction studies of DNA fibres
o Cross pattern with short lines = characteristic of helix
o Spacing of lines suggested dimension
o Diffraction patterns suggested two intertwining helixes
- Edwin Donohue proposed that bases are perpendicular to sugar backbone and in the enol form
- Erwin Chargaff discovered Purines = Pyramidines in 1:1 ratio
GENETIC CODE
Set of instructions (exists in the form of genes) that enable us to
- Live
- Reproduce
- Pass information to next generations
Once the package is opened and the zygote is formed it develops a lifetime dynamic relationship with its
environment
Genes: linear string of nucleotides that contain information to produce molecules needed
DNA molecules exists in cells at different packaging levels in the form of chromatin
- Chromatin can be loose/open or compact
- Compact chromatin is packaged as chromosomes
NUCLEOTIDE COMPOSITION
1. Sugar
2. Phosphate
3. Base
a. Planar, conjugated rings
b. Uncharged under physiological conditions
c. Can gain or lose a proton at near physiological pH
d. pKas values correspond to the pH where this transition occurs
,NUCLEIC ACID: store and transmit genetic information (DNA or RNA)
- DNA: stores genetic information in all cells and some viruses
o Information on how, when, and where to produce each kind of protein is carried in the genetic
material
o 3D structure of 2 helical strands coiled around a common axis
o Formed a double helix
o Strands are formed from nucleotides
- RNA: stores some genetic information, forms chromosomes of other viruses, decodes the genetic
information, catalyses key reactions during protein synthesis
NUCLEOSIDE: Sugar + base
- Formed by glycosylic linkage of sugar and base
NUCLEOTIDE: 5-C Sugar + base (pyramidine or purine) + phosphate groups
- Formed by phosphate ester linkage of phosphates to a nucleoside
- RNA and DNA differ in the sugar the nucleotide contain
- Building blocks of nucleic acids
PYRIMIDINES AND PURINES
Bases in nucleotides are derivative over pyrimidines or purines
1. Pyrimidines: single ring containing 4C and 2N → uracil, thymine and cytosine
2. Purine: fused pyrimidine-imidazole ring system → adenine and guanine
Both bases are unsaturated with conjugated double bonds → makes the rings planar and accounts for their
ability to absorb ultraviolet light
- Both are weak bases that are relatively insoluble in water at physiological pH
- In the cell, most bases occur as constutuents of nucleotides and polynucleotides → highly water soluble
Adenine + cytosine (cyclic amidines) → exist in either amino or imino forms
Guanine + thymine + uracil (cyclic amides) → lactam (keto) or lactim (enol) forms)
POLYNUCLEOTIDE
A linear sequence of nucleotides joined by phosphodiester bonds
Sugar + phosphate backbone – repeat unit
Base attached varies along the strand
, DNA DOUBLE HELIX 3-D CONFORMATION
- Two single DNA strands associate via non-covalent hydrogen and Van Der Waals bonds to form double-
stranded DNA in a 5’ to 3’ orientation
- Base pairs with their complementary base
o A:T (2 H bonds)
o C:G (3 H bonds
▪ Watson-crick base pairs
- Sequence of one strand dictates sequence of the other strand = strands are complementary to one
another
- Antiparallel
- Chargaffs rule: purines:pyramidines = 1:1
- Exists primarly in B-DNA form
o Ability of DNA to adopt said structure is advantageous for information accessibility and
packaging, making DNA the information store and not RNA (Travers and Muskhelishvili, 2015)
▪ Analogue information determines the sequence-dependent physiochemical properties
of DNA
• Stiffness and susceptibility to strand separation
PHYSICAL PROPERTIES OF DOUBLE HELIX
- Most energetically favourable conformation is for two strands to wind around one another in right-
handed double helix
o Every ~10.5 bp (B-form)
- Sugar-phosphate backbone is hydrophilic and lies outside the helix
- Base pairs are hydrophobic and lie on inside
o Forms base stacking
- Base stacks bind asymmetrically with sugar-phosphate backbone forming major (~13A) and minor
(~9A) groove
- Edges of base pairs are exposed in major and minor grooves
o Helps in DNA stability and protein interactions during replication, transcription, recombination
and repair