THIRD WEEK
Chemical structure of nucleosides
nucleotides and their nomenclature
Gihan E-H Gawish, MSc, PhD
Ass. Professor
Molecular Genetics and Clinical
Biochemistry
KSU
and
Learning objectives:
KNOW THE STRUCTURES AND NOMENCLATURE
OF THE BUILDING BLOCKS OF NUCLEIC ACIDS
•
PURINE AND PYRIMIDINE
• BASESNUCLEOSIDE NUCLEOTIDES
• RIBONUCLEOTIDES AND DEOXYRIBONUCLEOTIDES
Nucleotide = monomers that make up DNA and RNA
Three components
1. Pentose (5-carbon) sugar
DNA = deoxyribose
RNA = ribose
(compare 2’ carbons)
2. Nitrogenous base
Purines
Adenine
Guanine
Pyrimidines
Cytosine
Thymine (DNA)
Uracil (RNA)
3. Phosphate group attached to 5’
carbon

A base + a sugar is a
nucleosid

nucleoside + phosphate is
a nucleotide

(nucleotides
named
by
nucleoside plus number of
phosphates
–
adenosine
diphosphate)
Nitrogen

on C-1’ position
Phosphate commonly on C5’
Nucleosides and Nucleotides
Portion of polynucleotide chain of deoxyribonucleic acid (DNA). The inset shows the
corresponding pentose sugar and pyrimidine base in ribonucleic acid (RNA).
Animation
DNA structure, showing the nucleotide bases cytosine (C), thymine (T), adenine (A), and
guanine (G) linked to a backbone of alternating phosphate (P) and deoxyribose sugar (S)
groups. Two sugar-phosphate chains are paired through hydrogen bonds between A and T and
between G and C, thus forming the twin-stranded double helix
Nucleotides are linked by phosphodiester bonds to form polynucleotides
Phosphodiester Bonds
 Covalent bond between the
phosphate group (attached to 5’
carbon) of one nucleotide and the
3’ carbon of the sugar of another
nucleotide.
 This bond is very strong, and
for this reason
remarkably stable.
DNA
is
 DNA can be boiled and even
autoclaved without degrading
5’ and 3’
 The ends of the DNA or RNA
chain are not the same.
 One end of the chain has a 5’
carbon and the other end has a 3’
carbon.
5’ end
3’ end
James D. Watson & Francis H. Crick - 1953
Double Helix Model of DNA
Two sources of information:
1.
Base composition studies of Erwin Chargaff
•
indicated double-stranded DNA consists of ~50% purines
(A,G) and ~50% pyrimidines (T, C)
•
amount of A = amount of T and amount of G = amount of C
(Chargraff’s rules)
•
%GC content varies from organism to organism
Examples:
%A
%T
%G
%C
%GC
Homo sapiens
Zea mays
Drosophila
Aythya americana
31.0
25.6
27.3
25.8
31.5
25.3
27.6
25.8
19.1
24.5
22.5
24.2
18.4
24.6
22.5
24.2
37.5
49.1
45.0
48.4
James D. Watson & Francis H. Crick - 1953
Double Helix Model of DNA
Two sources of information:
2.
X-ray diffraction studies - Rosalind Franklin & Maurice Wilkins
Conclusion-DNA is a helical structure with
distinctive regularities, 0.34 nm & 3.4 nm.
Fig. 2.12
Double Helix Model of DNA: Six main features
1.
Two polynucleotide chains wound in a right-handed (clockwise)
double-helix.
2.
Nucleotide chains are anti-parallel:
3.
Sugar-phosphate backbones are on the outside of the double
helix, and the bases are oriented towards the central axis.
4.
Complementary base pairs from opposite strands are bound
together by weak hydrogen bonds.
5’  3’
3’  5’
A pairs with T (2 H-bonds), and G pairs with C (3 H-bonds).
e.g.,
5’-TATTCCGA-3’
3’-ATAAGGCT-3’
5.
Base pairs are 0.34 nm apart. One complete turn of the helix
requires 3.4 nm (10 bases/turn).
6.
Sugar-phosphate backbones are not equally-spaced, resulting
in major and minor grooves.
Animation
1962: Nobel Prize in Physiology and Medicine
James D.
Watson
Francis H.
Crick
Maurice H. F.
Wilkins
What about?
Rosalind Franklin
RNA (A pairs with U and C pairs with G)
Examples:
mRNA
tRNA
rRNA
snRNA
messenger RNA
transfer RNA
ribosomal RNA
small nuclear RNA
RNA secondary structure:
Yeast Alanine tRNA
single-stranded
Function in
transcription
(RNA processing)
and translation
Organization of DNA/RNA in chromosomes
Genome = chromosome or set of chromosomes that contains all the
DNA of an organism (or organelle) possesses
Viral chromosomes
1. single or double-stranded DNA or RNA
2. circular or linear
3. surrounded by proteins
TMV
T2 bacteriophage
 bacteriophage
Prokaryotic chromosomes
1. most contain one double-stranded circular
DNA chromosome
2. others consist of one or more chromosomes
and are either circular or linear
3. typically arranged in a dense
clump in a region called the nucleoid
Problem:
Measured linearly, the Escherichia coli genome (4.6 Mb) would be 1,000
times longer than the E. coli cell.
The human genome (3.4 Gb) would be 2.3 m long if stretched linearly.
Solutions:
1. Supercoiling
2.
Looped domains
DNA double helix is twisted in space about its
own axis, a process is controlled by
topoisomerases (enzymes).
(occurs in circular and linear DNA molecules)
Fig. 2.22
More about genome size:
C value= total amount of DNA in the haploid (1N)
genome
Varies widely from species to species and shows no
relationship to structural or organizational complexity.
Examples
C value (bp)

T4
HIV-1
E. Coli
Lilium formosanum
Zea mays
Amoeba proteus
Drosophila melanogaster
Mus musculus
Canis familiaris
Equus caballus
Homo sapiens
48,502
168,900
9,750
4,639,221
36,000,000,000
5,000,000,000
290,000,000,000
180,000,000
3,454,200,000
3,355,500,000
3,311,000,000
3,400,000,000
Eukaryotic chromosome structure
Chromatin
complex of DNA and chomosomal proteins
~ twice as much protein as DNA
Two major types of proteins:
1.
Histones
abundant, basic proteins with a positive charge
that bind to DNA
5 main types: H1, H2A, H2B, H3, H4
~equal in mass to DNA
evolutionarily conserved
2.
Non-histones
all the other proteins associated with DNA
differ markedly in type and structure
amounts vary widely
>> 100% DNA mass
<< 50% DNA mass
Packing of DNA into chromosomes:
1.
Level 1
Winding of DNA around histones to create a
nucleosome structure.
2.
Level 2
Nucleosomes connected by
strands of linker DNA like
beads on a string.
3.
Level 3
Packaging of nucleosomes into
30-nm chromatin fiber.
4.
Level 4
Formation of looped domains.
More about different types of DNA you should know about:
•Centromeric DNA (CEN)
Center of chromosome, specialized
sequences function with the
microtubles and spindle apparatus
during mitosis/meiosis.
•Telomeric DNA
At extreme ends of the chromosome,
maintain stability, and consist of
tandem repeats. Play a role in DNA
replication and stability of DNA.
Repeated DNA:
•Unique-sequence DNA
Often referred to as single-copy and
usually code for genes.
•Repetitive-sequence DNA
May be interspersed or clustered
and vary in size.
SINEs
short interspersed repeated sequences (100-500 bp)
LINEs
long interspersed repeated sequences (>5,000 bp)
Microsatellites
short tandem repeats (e.g., TTA|TTA|TTA)
Quiz
HTTP://WWW.WILEY.COM/COLLEGE/FOB/QUI
Z/QUIZ23/QUIZZER23.HTML
Please, Send the online Quiz to my email;
ggawish@ksu.edu.sa