The Central Dogma of Biology

Biological length scale

Chemical bond 1Å (10-10 m)

DNA RNA Protein Amino acid 10 Å (10-9 m)
Globular protein 100 Å (10-8 m)
Virus 1000 Å (10-7 m)
Cell nucleus 1 µm (10-6 m)
Bacterial cell 5 µm (10-5 m)
Chromosome DNA 10 cm (10-1 m)

Nucleic Acids and Nucleic Acid Structure

Nucleotides: Nitrogenous base + sugar + phosphate

Primary structure similar
Nitrogenous bases:
Sugar phosphate backbone
PURINES
Major difference in the type of sugar and base
PYRIMIDINES attached

Nucleic Acids and Nucleic Acid Structure
Two major types of nucleic acids, DNA and RNA.
Sugars used are:
Nucleic Acids and Nucleic Acid Structure
The nucleic acids are made up of polymers
of four different nucleotide residues each.
RNA uses AMP, CMP, GMP, and UMP
DNA use the deoxy forms:
dAMP, dCMP, dGMP, and dTMP.

The two nucleic polymers differ by both the

2‘ functional group (-OH or -H) and the use
of either uridine or thymine as the fourth
base.

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 Base families Base families

Purines: Pyrimidines:
Fused 6 & 5 membered hetero N7 C6 Six membered CN-ring, C4
C5
CN-ring system, usually C5 usually unsaturated. Three
unsaturated. Two common C8 N1
common purines found in C6
N3
purines in biological systems, biological systems:
both used in DNA and RNA, N9 two (C & T) used in DNA, and
C4 C2 N1
as well as in energy carriers C2
two (C & U) used in RNA
(ATP & GTP). N3
· cytosine Pyrimidine
· adenine
Purine · uracil
· guanine
· thymine

Base families β-N-glycosidic bond

NH2 O Nitrogen base
7 6 Pentose sugar
N 5 1 N N
N N NH
8 Phosphate group
4 2 N N
9N N N H
N NH2
H H
3
Purine Adenine (A) Guanine (G)
NH2 O
O
4
3 H3C
OH ribose
5 N N NH
NH

6 2
H deoxyribose
N1 N O N O
H N O
H H H Nucleoside
Pyrimidine Cytosine (C) Thymine (T) Uracil (U)

Nucleotide

Example:
Nucleotide
Nucleobase Nucleoside

NH2
NH2 NH2
7 6 N N
N 5 N1
N N
8 N N
HO 9 O N N
N 4 N 2
O 5'
9
H 3 H H -O P O O
H H O- 4' H 3' H 1'
OH H H H
Adenine OH 2'H
2’-deoxyadenosine
2’-deoxyadenosine-5’-monophosphate

2
 Conformational considerations

The backbone of RNA and DNA consists of the

alternating phosphate-ribose (or 2'-deoxyribose)
chain.

Conformational variation arises from restricted

bond rotations within the sugar ring, giving rise to
different ribose ring pucker, and torsional angles
at bonds connecting phosphate to ribose.

Torsion at the phosphodiester bonds

Rotation about the C-1'
bond allows two
Phosphate is tetrahedral orientations:
like carbon, so favoured
conformations occur at anti- extends the base and
±g (gauche, ±60o) or t pentose rings in opposite
(extended, 180o). directions. For pyrimidines,
this means that O-2 faces
away from the pentose.
α (bond to 5'-O) and ζ
(bond to previous 3'-O). syn- orients the base and
the pentose in the same
direction.

Free purine nucleosides,

in particular guanosine,
favour the syn- orientation,
but adopt the common
anti- orientation within
most DNA and RNA
helices.

Pyrimidines adopt anti-

orientation almost
exclusively, because of
steric interference
between O-2 and C-5' in
the syn- orientation,

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In synthesizing a nucleic acid polymer from individual
monomers, the 3'-hydroxyl group of one nucleotide
attacks the α-phosphate of a nucleotide triphosphate,
displacing a pyrophosphate with the cleavage of an • a polymer made by linking nucleotides
anhydride bond: via phosphodiester bonds.

• these bonds are synthesized by the

attack of an alcohol residue from ribose on
the α-phosphate to release a diphosphate
residue (which is subsequently hydrolyzed
to phosphate)

Watson Crick Base pairing

¾ Nucleotides are linked

by phosphodiester bonds

¾ Strand has a direction

(5'→3')

Hoogsteen Base pairing

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 DNA Components

Four nucleotide types:

• Adenine
• Guanine
• Cytosine
• Thymine

Source: Mathews & van Holde

Hydrogen bonds:
• A-T
• C-G

The Double Helix

Source: Alberts et al