FAR EASTERN UNIVERSITY – NICANOR REYES MEDICAL FOUNDATION BIOCHEMISTRY AUGUST 2019

LESSON 4: NUCLEIC ACIDS

DNA (Deoxyribonucleic Acid) - In the nucleus.

RNA (Ribonucleic Acid) - In the ribosome.

Nucleic Acid
 A biopolymer containing three types of
monomer units:
 A sugar (a pentose), either D-ribose or
2-deoxy-D-ribose.
 A base derived from purine or
pyrimidine.
 A phosphate.

Pyrimidine/Purine Bases
 The structures of pyrimidine and purine:
Nucleosides
 Nucleoside = sugar + base
 D-ribose or 2-deoxy-D-ribose covalently
bonded to a nucleobase by a β-N-
glycosidic bond.
 No phosphate group.

Other Bases
 Less common bases can occur. Nucleosides + PO4
 Principally but not exclusively, in transfer Bases NTPs
(Nucleotide)
RNAs. A Adenosine AMP ATP
G Guanosine GMP GTP
C Cytidine CMP CTP
T Thymidine TMP TTP
U Uridine UMP UTP

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Nucleotides Nucleic Acids

 Nucleotide: PO4 + sugar + base  Polymerization of nucleotides leads to
 A nucleoside + phosphoric acid nucleic acids.
 Phosphoester bond with an -OH of the  Linkage is repeated.
sugar, most commonly either the 3’-OH  (3’,5’-phosphodiester bond)
or the 5’-OH.
 Name based on parent nucleoside with
a suffix “monophosphate”.

Levels of Structure:
 1o Structure – The order of bases on
the polynucleotide sequence; the order
of bases specifies the genetic code.
 2o Structure – The three-dimensional
conformation of the polynucleotide
backbone.
 3o Structure – Supercoiling.
 4o Structure – Interaction between DNA
and proteins.

Deoxyribonucleic Acids, DNA:

1. Primary Structure
 The sequence of bases along
the sugar-phosphodiester
backbone of a DNA molecule.
 Base sequence is read from the
5’ end to the 3’ end.

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 System of notation single letter

(A, G, C and T).

or

2. Secondary Structure
 The ordered arrangement of
nucleic acid strands.
o The double helix model of
DNA 2o structure was
proposed by James
Watson and Francis Crick  T-A Base Pairing
in 1953. o Base pairing is
 Double Helix: complementary.
o Two antiparallel o A major factor stabilizing
polynucleotide strands the double helix is base
are coiled in a right- pairing by hydrogen
handed manner about the bonding between T-A and
same axis. between C-G.
o Structure based on x-ray o T-A base pair comprised
crystallography. of 2 hydrogen bonds.

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 G-C Base Pair  Base Stacking

o G-C base pair comprised o Bases are hydrophobic
of 3 hydrogen bonds. and interact by
hydrophobic interactions.
o In standard B-DNA, each
base rotated by 32o
compared to the next.

Forms of DNA 2o Structure

a. B-DNA
 Considered the physiological
form.
 A right-handed helix, diameter
11A.
 10 bases pairs per turn (34A) of
the helix.
 Occurs in nature.
b. A-DNA
 A right-handed helix, but thicker
than B-DNA. 3. Tertiary Structure (in Prokaryotes)
 11 base pairs per turn of the  The 3-D arrangement of all atoms
helix. of a nucleic acid.
 Has not been found in vivo. o Commonly referred to as
supercoiling.
c. Z-DNA  Circular DNA:
 A left-handed double helix. o A type of double-stranded
 May play a role in gene DNA in which the 5’ and 3’
expression. ends of each strand are
joined by phosphodiester
bonds.

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 During DNA replication, the

double strands must separate.
 This causes torsional strain to the
double helix that would the DNA
polymerase, and stop synthesis.

 Topoisomerases:
o Enzymes that relax
supercoiling in closed
circular DNA.
 Class I: Cut the
phosphodiester 4. Tertiary Structure (in Eukaryotes)
backbone of one  Histone:
strand, pass the o A protein, particularly rich
end through, and in the basic amino acids
reseal. Lys and Arg; found
 Class II: Cut both associated with eukaryotic
strands, pass DNA.
some of the  5 main types: H1,
remaining DNA H2A, H2B, H3, H4
helix between the  Chromatin:
cut strands, and o DNA molecules wound
reseal. around particles of
o DNA Gyrase: histones in a beadlike
 A bacterial structure.
topoisomerase II.  Each “bead” is a
nucleosome.
 Nucleosome
consists of: DNA
wrapped around
histone core.

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Denaturation of DNA
 Denaturation
 Disruption of 2o structure.
 Most commonly by heat
denaturation (melting).
 Double helix unwinds when DNA
is denatured.
3o Structure (Supercoiling) in Eukaryotic  Renaturation
DNA o Double helix can be re-formed
 The lowest level is the nucleosome, with slow cooling and annealing.
consisting of 150.bp of DNA wrapped 1
¾ times around a core of 8 histone
proteins. It forms a string of beads.
 The nucleosomes coil up into a 30-nm
chromatin fiber.
 During cell division, chromatin fibers are
attached in loops of variable size to a
protein scaffold.
 Further coiling gives the compact
structures seen in metaphase.

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