Unit 7

NUCLEIC ACIDS:
How Structure Conveys Information
maidliu 03.07.2017
Historical Perspective

• In 1968, Friedrich Miescher isolated “nuclein” and

“protamine” from salmon sperm.

• In 1944, Oswald
Avery, Colin
MacLeod, and
Maclyn McCarty
showed that DNA
from pathogenic
strains of bacterium
Pneumococcus could
be transferred into
nonpathogenic
strains, making them
pathogenic.
Historical Perspective

• In 1952, Alfred Hershey and Martha

Chase proved that DNA, and not
protein, is the genetic material of T2
bacteriophage.
Historical Perspective
• James Watson and Francis Crick proposed the model of the
double helix of DNA in 1953.

Structure of DNA James D. Watson Francis C. Crick

Nucleic Acids

• NUCLEIC ACIDS: biomolecules that store information for

cellular growth and reproduction.

• TYPES of NUCLEIC ACIDS:

• Deoxyribonucleic acid (DNA)
• Ribonucleic acid (RNA)

• These are polymer consisting of

long chains of monomers called
nucleotides.

• Each nucleotide unit is made up

of:
• Nitrogen heterocyclic base
• Pentose sugar
• Phosphate residue
Structure of a nucleotide
Nucleotide bases
• Nucleotide bases: derivatives of pyrimidine/purine base
Nucleotide bases: Properties
• Aromatic
• Strongly absorbs uv light
• Exhibits keto-enol tautomerism

Tautomeric forms of nucleobases Absorbance spectrum of nucleobases

Composition of Nucleoside
• Pentose sugar and nucleotide base linked by N-glycosidic
bond to form a nucleoside.

• Ribonucleoside: β-D-ribose sugar (2’ –OH)

• Deoxyribonucleoside: β-D-2-deoxyribose (2’ –H)

• Glycosidic bond between

sugar and base:
• Purine: βC1’ – N9
• Pyrimidine: βC1’ – N1

• Naming of nucleoside:
• Purine ends with – sine
• Pyrimidine – dine
Structure of (deoxy)ribonucleoside
Composition of Nucleotide

• Nucleotide is a nucleoside with one or more phosphate

groups covalently bound (ester bond) to the 3’- or 5’-
position of the pentose.

Phosphate ester bonds

Deoxyribonucleotides Ribonucleotides
(containing deoxyribose) (containing ribose)
Nucleic Acid: Structure

• 3’,5’-Phosphodiester bonds link

nucleotide residues in nucleic acid.
• Direction of the polynucleotide
strand: 5’ → 3’

Formation of a phosphodiester bond

Primary Structure of Nucleic Acid

• The sequence of bases

along the pentose-
phosphodiester backbone of
the nucleic acid.
• Base sequence is read from
the 5’ end to the 3’ end
• System of notation single
letter (A,G,C,U and T)

Schematic representation of nucleotide sequence

5’ ACGTA 3’
DNA: Secondary Structure

• B-DNA: the physiological form

• It is made up of two, antiparallel

polynucleotide strands that are
coiled to each other to form a
right-handed helix.

• The sugar-phosphate backbone

(negatively charged) are on the
outside of the helix.

• The bases are approximately

perpendicular to the axis of the
helix and are stacked one top of
another like a pile of plates.
DNA: Secondary Structure

• Hydrogen bonding between

complementary base pairs (A-T
or G-C) holds the two strands
together.
• A-T bp 2 H-bonds; G-C bp, 3 H-
bonds

• There are three major forces

that contribute to stability of helix
formation.
• H-bonding in base pairing
• Hydrophobic interactions in
base stacking
• Dipole-dipole interactions
DNA: Secondary Structure

• The spaces between adjacent turns

of the helix form 2 grooves; the
wider major groove and the narrow
minor groove.

• Diameter of the DNA： 2 nm

• Distance between two bp: 0.34 nm;
• Each turn of the helix involves 10
base pairs, 3.4 nm.
Forms of DNA
• B-DNA
• A-DNA
• DNA molecules at low
humidity
• right-handed helix, but
thicker than B-DNA
• 11bp per turn of the helix
• has not been found in vivo
• Z-DNA
• a left-handed double helix
• Usually occurs in alternating
purine-pyrimidine bases
• may play a role in gene
expression
Forms of DNA
DNA: Tertiary Structure

• Supercoiling: further coiling and twisting of

DNA helix.
• Topoisomerase: capable of cutting and
rejoining the DNA ends to produce
supercoils
• Negative/Positive supercoils
• Prokaryotic DNA is circular while eukaryotic
DNA is linear
DNA: Quaternary Structure

• Eukaryotic DNA is long (2m) and

linear. It has to packed in a tight
structure in the nucleus.
• Chromatin: DNA molecules
wound around particles of
histones in a beadlike structure
(nucleosome).
• Histone: a protein rich in the
basic aa Lys and Arg; found
associated with eukaryotic DNA
• Topological changes induced by
supercoiling accommodated by
histone-protein component of
chromatin.
Denaturation and Renaturation of DNA
• When DNA duplex is subjected to conditions of pH,
temperature or ionic strength that disrupt H-bonds; the
strands are readily separated. This results to denaturation
of DNA.

• Melting temperature (Tm)

is a measure of the base
composition of DNA. Tm
increases linearly with the
proportion of G-C bps in the
DNA.
• As strands separate,
absorbance at 260 nm
increases.
Effect of change in temperature to DNA
Denaturation and Renaturation of DNA
• Double helix unwinds when DNA is denatured
• Can be re-formed with slow cooling and annealing

Denaturation and renaturation of DNA

RNA: Structure and Function

• In general, RNA is single stranded.

• RNA molecules are classified according to their structure
and function.
tRNA
• Transfer RNA, tRNA:
• the smallest kind of the three
RNAs
• a single-stranded
polynucleotide chain between
73-94 nucleotide residues
• carries an amino acid
at its 3’end
• intramolecular hydrogen
bonding occurs in tRNA

Structure of tRNA
rRNA
• Ribosomal RNA, rRNA: a ribonucleic acid found in ribosomes, the site
of protein synthesis
• Ribosomes consist of 60 to 65% rRNA and 35 to 40% protein
• Ribosomes made up of two subunits.
• Analyzed by analytical ultracentrifugation; characterized by
sedimentation coefficients, in Svedberg units (S)

Components of prokaryotic
and eukaryotic ribosomes
mRNA
• Messenger RNA, mRNA: a ribonucleic acid that
carries coded genetic information from DNA to
ribosomes for the synthesis of proteins
• present in cells in relatively small amounts and very
short-lived
• single stranded
• biosynthesis is directed by information encoded on
DNA
• a complementary strand of mRNA is synthesized along
one strand of an unwound DNA, starting from the 3’
end