By
Dr Anitha
Learning objectives :
At the end of lectures on this topic, I MBBS
students should be able to:
• Explain what are nucleosides & nucleotides
• Describe the composition, structure of DNA,
based on the Watson-Crick model and
explain the function of DNA.
• List the different types of RNA, describe the
composition, structures and explain the
function of each.
2
Nucleic acids are
Macromolecules present in
all cells.
Both eukaryotes and
prokaryotes
Present mostly in nucleus
but also in cytoplasm and
mitochondria
Important for protein
synthesis and inheritance
Codes genetic information
Takes part in cell division
Polymers of monomeric units called NucleotidesPolynucleotides
Two types – Based on the sugar
present
Deoxyribonucleic Acid
(DNA)
Transcription
DNA
Replication
DNA
Ribonucleic Acid
(RNA)
Translation
RNA
Protein
Location –
DNA – Nucleus & Mitochondria(small amount)
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RNA –Cytoplasm (90%) & Nucleolus
• Building blocks of Nucleic acids
• Composed of
1. Sugar
2. Nitrogenous Base
3. phosphate group
• Phosphate esters of 5 carbon sugar (Pentose)
in which a nitrogenous base is covalently
linked to C1 of sugar residue
• They are phosphorylated nucleosides
Nucleotide structure
5′
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a) Nitrogenous base
2 Major types found in nucleotides:
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Purine bases
6- amino purine
2 – amino ,6-oxo purine
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Pyrimidine bases
in RNA
in DNA & RNA
in DNA
except tRNA
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Minor bases (modified bases) found in
nucleotides in small amounts:
Examples:
• 7-methylguanine
• 5-methylcytosine
• Dihydrouracil (DHU)
Unusual bases help in recognition by
specific enzymes or protect from being
degraded by nucleases .
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• Bases occurring freely as metabolic
intermediates
Examples:
Xanthine
Hypoxanthine
Uric acid (end product of purine catabolism)
• Bases present in plants
Examples:
Caffeine (of coffee)
Theophylline (of tea)
Theobromine [of cocoa]
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b) Pentose sugars
present in nucleotides,
RNA and DNA
Ribose in RNA
2-deoxy ribose in DNA
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c) Phosphate group
• is attached to pentose sugar (5′
hydroxyl group) by an ester linkage in a
nucleotide
• 1, 2 or 3 phosphate group/s may be
present in a nucleotide
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Nucleoside
It consists of:
Nitrogenous base
Sugar
(purine/pyrimidine)
N-glycosidic bond
• Ribonucleoside contains ribose sugar
• Deoxyribonucleoside contains deoxy
ribose sugar
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Examples
Base
Ribonucleoside
Adenine
Guanine
Cytosine
Uracil
Thymine
Adenosine
(Adenine + Ribose)
Guanosine
(Guanine + Ribose)
Cytidine
(Cytosine + Ribose)
Uridine
(Uracil + Ribose)
-
Deoxyribonucleoside
Deoxyadenosine
(Adenine + Deoxyribose)
Deoxyguanosine
(Guanine + Deoxy ribose)
Deoxycytidine
(Cytosine + Deoxyribose)
Thymidine
(Thymine + Deoxyribose)
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Nucleotide
• is phosphorylated nucleoside
Nitrogenous base
Sugar
Phosphate/s
N-glycosidic bond
ester linkage
• can exist as
-Nucleoside monophosphate (NMP),
-Nucleoside diphosphate (NDP) or as ( 1 high energy
bond )
-Nucleoside triphosphate (NTP)(2 high energy bonds
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Examples:
Ribonucleotide
Deoxyribonucleotide
AMP
(adenosine + phosphate)
GMP
(guanosine + phosphate)
CMP
(cytidine + phosphate)
UMP
(uridine + phosphate)
-
dAMP
(deoxy adenosine + phosphate)
dGMP
(deoxy guanosine + phosphate)
dCMP
(deoxy cytidine + phosphate)
TMP
(thymidine + phosphate)
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Biologically important free Nucleotides & their functions
Functions
Building blocks of
nucleic acids : DNA
RNA
Sources of energy
Examples of nucleotides
dAMP, dGMP, dCMP, TMP
AMP, GMP, CMP, UMP
ATP (universal energy currency), GTP
Second messengers
cyclic AMP (cAMP) (FSH,
LH,TSH,Corticotropin, Vasopressin,
Glucagon ,PTH), cGMP
Donors of certain
groups
Phosphoadenosine phosphosulfate PAPS
S-Adenosyl methionine (SAM)
UDP glucose
CDP choline
+
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Synthetic analogues of Purine,
Pyrimidine Nucleotides:
Therapeutic uses
Anticancer agents
Examples
6-mercaptopurine,
5- fluorouracil
Immunosupressants
Azathioprine
Treatment of gout
Allopurinol
Antiviral agents
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Answer this:
 Which of the following nucleotides
YOU
functions as a THANK
second messenger?
a. FAD
b. PAPS
c. dGMP
d. cAMP
Genetic material in both Prokaryotes and Eukaryotes
Prokaryotes
Lack separation from
cytoplasm
Absence of nuclear
membrane
Not organised with proteins
Eukaryotes
Separate from cytoplasm
Nuclear membrane present
Organised with proteins Chromatin
Less than 0.1% is present in Mitochondria
• Definition
DNA is a polymer of
deoxyribonucleotides
(i.e. it is a polynucleotide).
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•
Location
Mitochondria: Circular DNA
Nucleus:
Linear DNAchromosomes
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Watson &
Crick
1953
First described the
structure of DNAA milestone in
modern biology
(Noble Prize 1962)
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Structure of DNA:
Watson and Crick model
Salient features:
• DNA is double-stranded
• Each DNA strand has a linear arrangement
of its four nucleotides (monomeric units);
dAMP (A),
dGMP (G),
dCMP (C) and
TMP (T)
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Primary structure of each DNA strand
• It is the sequence of
deoxyribonucleotides
in the polynucleotide chain
E.g. A-G-T-C……..
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Nucleotide 1
P
3’, 5’
Phospho
diester
P
bond
Deoxy
ribose
3′ end sugar
5′ end
Base, A
Nucleotide 2
Deoxy
ribose
sugar
Base, G
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Watson and Crick model
5′- OH
Phospho
diester
bonds
Strand
1
Strand
2
H bonds (2)
3′- OH
H bonds (3)
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Backbone formed by Sugar &Phosphate
Core by Nitrogenous bases
Two polar ends – 3’ & 5’ ends
Inspired by DNA….!!
Spiral
staircase
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DNA contains two polynucleotide
chains
B-DNA
Polynucleotide chains have 5’ end
and 3’ end
Two polynucleotide chains are coiled
round a common axis
Two polynucleotide chains are
antiparallel
Right handed double helix
Sugar and phosphate forms the
backbone - Hydrophilic
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Purine and pyrimidine
bases are Hydrophobic
Purines – A& G
Pyrimidines –C&T
Purine and pyrimidine
bases present inside
the core – (STACKED)
B-DNA
Has got
Major groove
and
Minor groove
Where proteins bind to
DNA
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Secondary structure of DNA
• It refers to the coiling of double-stranded
DNA molecule
• Coiling is right- handed
Right handed double helix
of DNA
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H bonds hold the two strands
in a double-helix structure
Adenine base pairs with
Thymine forming two
hydrogen bonds
A=T
Guanine base pairs with
Cytosine forming three
hydrogen bonds
G=C
B-DNA
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Hydrogen bonds
The amount of
Adenine = Thymine
Guanine = Cytosine
The amount of
Purines = Pyrimidines
Chargaff’s Rule
B-DNA
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Diameter of the double helix
is 20A0
One turn of double helical
DNA travels a distance of
34 A0
One turn contains 10 base
pairs
Distance between the
adjacent nucleotides is
3.4 A0
B-DNA
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Learning check point:
Which of the following statements on DNA
double helical structure is true?
a. The two strands run in parallel direction
b. The two strands are held together by phosphodiester bonds
c. H bonds are formed between complementary
base pairs
d. The strands are composed of ribonucleotides
B-DNA-Most common
Right – handed
10 base pairs per one
full turn
Z-DNA
Left – handed
12 base pairs per one
full turn
A-DNA
Right – handed
11 base pairs per one
full turn
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25 A0
34A0
45 A0
12 base pairs
10 base pairs
11 base pairs
• Linear DNA double stranded structure – Human
DNA
• Circular DNA – Bacteria – no free ends
• Length – 1.74 meters when stretched
• Made compact to fit into nucleus- Supercoiling
• Supercoils – Right handed (positive)
Left handed (Negative)-common
• In prokaryotes – circular DNA with RNA
protein core
• In Eukaryotes more complicated
• 10000 fold shortening by supercoiling is seen
to fit into nucleus as chromosomes (23 pairs)
• During resting state – Chromatin
Cell division- Chromosomes
• A typical human cell contains DNA which is
approximately two meters long.
???
How do you get 2 m of DNA
into a 6 µm nucleus of a cell?
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Structural units of chromatin composed
of DNA (negatively charged)bound to
histones (positively charged) forming
octomers
DNA winds around the core of histones
DNA links between two nucleosomes continuously
Core Histone
H1 Histone
DNA
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Neighboring Nucleosomes are joined by ‘linker’DNA
(about 30 base pair long)
H1 Histone binds to linker DNA
Helps to pack nucleosomes into
a more compact structure
Core Histone
DNA
It resembles beads on a string
H1 Histone
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•10-nm fibril is probably further supercoiled
•Six or seven nucleosomes per turn to form the
30-nm chromatin fiber
DNA
Protein scaffolding
1400 nm
Nucleosome 10nm
30 nm
300 nm
Looped domains
700 nm
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Nucleosomes
Loops of chromatin
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DR. ASHOK KUMAR J.
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Genome
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chromosomes
(3 billion
base pairs)
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Function of DNA
• DNA contains genetic information
• The sequence of four nucleotides (A, T, G, C)
in DNA encodes genetic information.
• The code is read by copying stretches of
DNA into RNA by transcription.
• In DNA, about 10% is coding region and
non-coding region is about 90%.
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• Coding regions in DNA code for proteins,
RNA.
• Structural genes code for proteins; other
THANK YOU
genes code for RNA.
• The strand of DNA containing the code for
the protein is called Template strand;
opposite strand is Coding strand.
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Flow of genetic information
DNA 
RNA
Transcription
Central Dogma
of
Molecular Biology

Protein
Translation
Phenotype
(Physical characteristics)
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Melting of DNA
Annealing
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Differences between RNA and DNA
RNA
DNA
Seen in: cytoplasm, nucleus
Single stranded
Sugar is ribose
Usually has: 100-5000 bases
Pyrimidine: Uracil
Chargaff’s rule: not obeyed
Destroyed by alkali
Function:
Protein synthesis
Nucleus, mitochondria
Double stranded
Sugar is deoxyribose
Millions of base pairs
Thymine
Obeys Chargaff’s rule
Alkali-resistant
Contains genetic
information; basis for
heredity and evolution58
RNA (Ribonucleic acid)
• Definition:
RNA is a polymer of ribonucleotides joined
by 3′-5′ phosphodiester bonds and
generally single-stranded.
• RNA is involved in protein synthesis
• RNA is transcribed from genes present in
DNA
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Types of RNA
1.
2.
3.
4.
Messenger RNA (mRNA)
Transfer RNA (tRNA)
Ribosomal RNA(rRNA)
Small nuclear RNA(snRNA)
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1. Messenger RNA (mRNA)
• Mature mRNA is produced from
heteronuclear RNA (hnRNA) which is
transcribed from the DNA in nucleus.
• hnRNA is processed to form mRNA.
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Nucleus
Cytoplasm
Protein
mRNA
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Structure of mRNA
Codons
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prevents the hydrolysis of
mRNA by 5′ exonucleases
mRNA
Translated region
contains codons
for amino acids
7- methylguanosine
triphosphate
polymer of adenylate
nucleotides (20-250)
maintains intracellular
stability of mRNA
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Function of mRNA:
• It acts as a messenger,
and conveys
genetic information
from DNA to
protein synthesizing
machinery
in cytoplasm
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2. Transfer RNA (tRNA)
• At least 20 different types tRNAs exist
(at least one for each amino acid).
• Length is 74 -95 nucleotides
• (It was formerly called soluble RNA or
sRNA).
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Structure of tRNA
It resembles a clover leaf.
It has 4 arms:
1) Acceptor arm
2) Anticodon arm
3) D arm
4) TC arm ( = psi)
The arms have base-paired stems and
unpaired loops (no loop for acceptor arm).
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Attachment site
for the amino acid
Recognition site
for enzyme that
adds the amino acid
Recognition of triplet
codon of mRNA
tRNA contains
some unusual bases
Involved in binding
of tRNA to ribosome
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Function of tRNA:
• It is an adaptor molecule for the translation
of codons in mRNA into protein sequence.
• It does so by transporting (carrying) amino
acid to the site of protein synthesisribosomes.
Amino acid
Ribosomes
- mRNA
tRNA
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Met
tRNA
Anticodon
UAC
Codon
mRNA
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3. Ribosomal RNA (rRNA)
• rRNA and proteins complex to form
Ribosomes (nucleoproteins)
which are sites of protein synthesis.
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Eukaryotic Ribosome
Small subunit
40 S
18S rRNA +
33 proteins
80 S
Large subunit
60 S
5S, 28S, 58S rRNAs
+ 49 proteins
S = Svedberg units
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Function of rRNA
• rRNA is necessary for binding of mRNA to the
ribosome.
• 28s rRNA of 60S subunit has peptidyl
transferase activity for peptide bond
formation
(i.e. it is a Ribozyme; RNA as an enzyme).
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4. Small nuclear RNA (snRNA)
• Their sizes range from 90-300 nucleotides.
• They are named: U1, U2, U4, U5, U6 and U7
(rich in Uracil)
• They are examples for Ribozymes.
Function
• Involved in processing of mRNA (splicing)
and
• Gene regulation
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Learning check point:
The codon is found on _________ , and the
anticodon is found on ________ .
A. rRNA, mRNA
B. mRNA, tRNA
C. tRNA, mRNA
D. mRNA, rRNA
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An illustration of the functions of different RNAs
DNA
T
R
A
N
S
C
R
I
P
T
I
O
N
hnRNA
Splicing
mRNA Contains codons
for protein synthesis
snRNA
Forms
rRNA
Ribosome
TRANSLATION
Proteins
tRNAs
Amino acids
Aminoacyl-tRNAs
Transports
Amino acids
Proteins
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You have successfully completed
learning the topic:
Chemistry of Nucleotides
and Nucleic acids
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