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Nucleic Acid Chemistry
Growth and Development Block
Professor Nikhat Ahmed Siddiqui ,PhD
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[email protected]
http://genome.gsc.riken.go.jp/hgmis/graphics/slides/01-0085jpg.html
U.S. Department of Energy Human Genome Program, http://www.ornl.gov/hgmis.
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Objectives
Name the different types of Bases and sugars present in
Nucleic Acid
Define Nucleoside, nucleotide, DNA and RNA. Name the
structural component of each one.
Define Nuclear DNA, name its different forms and describe
the structure of its B-form.
Define nucleosome, describe its structure and list the
different stages of chromatin condensation till
chromosome.
Describe the general structure of RNA and name its
different types with the function of each type.
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General Structure of Nucleic Acid



DNA and RNA are long
chain polymers of small
compound called
nucleotides.
Each nucleotide is
composed of a base; sugar
(ribose in RNA or
deoxyribose in DNA) and a
phosphate group.
The phosphate joins the
sugars in a DNA or RNA
chain through their 5` and 3`
hydroxyl group by
phosphodiester bonds.
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Nitrogenous Bases
Pentose Sugar ‘Ribose’
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Nucleosides
Purine /pyrimidine base linked to sugar
residue is called Nucleoside eg:
Adenosine,Guanosine, Cytidine,Thymidine,Uridine
Linked to D-ribose as in RNA
Linked to D-2-deoxyribose as in DNA
Linkage in Purine or Pyrimidine Nucleosides
β-N-Glycosidic linkage.
The attachment of the C1 of the pentose sugar to 
N9 of purine or N1 of pyrimidine makes a
Nucleoside
Nucleotides
It is a nucleoside to which a phosphate group is
attached to the sugar molecule.
The nucleotides are Nucleoside-P
i.e. Base + sugar + phosphate
Nucleotides present in DNA:
dAMP deoxyadenylate ,
dGMP,dCMP,dTMP
Nucleotides present in RNA:
AMP adenylic Acid ,GMP,CMP,UMP
DNA is a double-stranded helix
James Watson and Francis Crick worked 
out the three-dimensional structure of DNA,
based on work by Rosalind Franklin
Figure 10.3A,
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Deoxyribonucleic Acid (DNA)
Deoxyribonucleic Acid
(DNA), the genetic
material of all cellular
organisms and most
viruses, the gigantic
molecule which is used to
encode genetic
information for all life on
Earth.
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Structure of DNA
A Polymer of Deoxyribonucleotides
Double –Stranded
Individual deoxynucleoside triphosphates are coupled by
Phosphodiester bonds.
ESTERIFICATION
- LINK 3’ CARBON of one RIBOSE with 5’ C of
another
- TERMINAL ENDS : 5’ AND 3’
A “DOUBLE HELICAL” STRUCTURE
- Common Axis for both HELICES
“- HANDEDNESS” OF HELICES
- ANTIPARALLEL RELATIONSHIP BETWEEN 2 DNA
STRANDS
PERIPHERY OF DNA: SUGAR-PHOSPHATE CHAIN
TRIPHOSPHATES ARE COUPLED BY PHOSPHODIESTER CORE
OF DNA BASES ARE STACKED IN PARALLEL FASHION
CHARGAFF’S RULES The ratio ofPyrimidine to purine is~1
A=T
G = C COMPLEMENTARY” BASE PAIRING between
two strands of DNA
DNA Structure
DNA contains only four types of
nucleotides, which are the building
blocks of nucleic acids.
Each nucleotide in DNA is made of:
a five carbon sugar•
Deoxyribose
a phosphate group
and one of four possible nitrogen bases
.
Chromosomal DNA is Packaged and
organized at several levels
Eukaryotic genes: DNA molecules
complexed with other proteins especially
basic proteins called histones, to form a
substance known as chromatin. A human
cell contains about 2 meters of DNA. So it
is tightly packed
Orders of DNA Structure
1.Primary:Linear sequence of
deoxyribonucleotide units
2.Secondary:Double Stranded Helix
3.Tertiary: double helix wrapped around
Histone Octamer toform a Nucleosome
4.Higher Orders: Formationof 30nm
Fibers (chromatin),Chromosomes
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FORCES THAT STABILIZE NUCLEIC
ACID STRUCTURES
SUGAR-PHOSPHATE CHAIN CONFORMATIONS
BASE PAIRING
BASE-STACKING,HYDROPHOBIC
IONIC INTERACTIONS
A always pairs with T, and G with C
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Hydrogen bonds between bases hold the 
strands together: A and T, C and G
Hydrogen bond
Ribbon model
Partial chemical structure
Computer model
Figure 10.3D
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STRUCTURE OF THE DOUBLE
HELIX
THREE MAJOR FORMS
B-DNA
A-DNA
Z-DNA
B-DNA IS BIOLOGICALLY THE MOST COMMON
RIGHT-HANDED
DIAMETER 20 Angstrom (A)
COMPLEMENTARY BASE-PAIRING (WATSON-CRICK)
A-T
G-C
10 base pair per turn repeating every 3.4nm
EACH BASE PAIR HAS ~ THE SAME WIDTH
10.85 A FROM C1’ TO C1’
A-T AND G-C PAIRS ARE INTERCHANGEABLE
“PSEUDO-DYAD” AXIS OF SYMMETRY
DNA Forms
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MAJOR AND MINOR GROOVES
MINOR

EXPOSES EDGE FROM WHICH C1’ ATOMS EXTEND
MAJOR


EXPOSES OPPOSITE EDGE OF BASE PAIR

THE PATTERN OF H-BOND POSSIBILITIES IS MORE
SPECIFIC AND MORE DISCRIMINATING IN THE
MAJOR GROOVE

GEOMETRY OF B-DNA
IDEAL B-DNA HAS 10 BASE PAIRS PER TURN
BASE THICKNESS
AROMATIC RINGS WITH 3.4 A
PITCH = 10 X 3.4 = 34 A PER COMPLETE TURN
Diameter is 2.37 nm
AXIS PASSES THROUGH MIDDLE OF EACH BP
MINOR GROOVE IS NARROW
MAJOR GROOVE IS WIDE
STRUCTURAL VARIANTS OF
DNA
DEPEND UPON:
SOLVENT COMPOSITION
- WATER
- IONS
BASE COMPOSITION
Nuclear DNA
Nuclear DNA is bound to basic proteins
called Histones.
DNA present in every nucleated cell and
carries the genetic information.
Chromosomal DNA is Packaged and
organized at several levels
Eukaryotic genes: DNA
molecules complexed with
other proteins especially basic
proteins called histones, to
form a substance known as
chromatin. A human cell
contains about 2 meters of
DNA. So it is tightly packed.
1. Nucleosomes: 10 nm
chromatin fibril
2. The 30nm fibril composed
of nucleosomes.
3.
Higher ordered structures:
a) Loop domains
b) SMC Proteins and control
of higher order domains.
-mitotic chromosome
condensation ,SMC proteins
and condensin
Structural Maintenance of chromosomes
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Chromatin Structure
(Nucleosomes)


Eukaryotic chromatin
is folded in several ways. The
first order of folding involves
structures called
nucleosomes, which have a
core of histones, around
which the DNA winds ( four
pairs of histones H2A,
H2B,H3 and H4 in a wedge
shaped disc, around it
wrapped a stretch of 147 bp
of DNA).
Nucleosomes are linked by
DNA linker wrapped around
H1.
Nucleosomes are the basic unit
of
eukaryotic chromosome structure
“Beads on a string “ 10 nm26
Chromatin fibril
The DNA in eucaryotes is tightly bound to an
equal mass of histones, which form a repeating
array of DNA-protein particles called
nucleosomes.
The nucleosome is composed of an octameric
core of histone proteins around which the DNA
double helix is wrapped.
Nucleosomes are usually packed together (with
the aid of histone H1 molecules) into quasi-regular
arrays to form a 30-nm fiber.
Despite the high degree of compaction in
chromatin, its structure must be highly dynamic to
allow the cell access to the DNA
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30 nm Chromatin fibril
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THE TOPOLOGY OF DNA
“SUPERCOILING” :
DNA’S “TERTIARY STRUCTURE
L = “LINKING NUMBER”
A TOPOLOGIC INVARIANT
THE # OF TIMES ONE DNA STRAND WINDS AROUND THE OTHER
L=T+W
T IS THE “TWIST
THE # OF COMPLETE REVOLUTIONS THAT ONE DNA STRAND MAKES
AROUND THE DUPLEX AXIS
W IS THE “WRITHE”
THE # OF TIMES THE DUPLEX AXIS TURNS AROUND THE
SUPERHELICAL AXIS
DNA TOPOLOGY
THE TOPOLOGICAL PROPERTIES OF DNA HELP US
TO EXPLAIN
DNA COMPACTING IN THE NUCLEUS
UNWINDING OF DNA AT THE REPLICATION FORK
FORMATION AND MAINTENANCE OF THE
TRANSCRIPTION BUBBLE
MANAGING THE SUPERCOILING IN THE ADVANCING
TRANSCRIPTION BUBBLE

Function of The DNA

Deoxyribonucleic Acid (DNA), the gigantic
molecule which is used to encode genetic information
for all life on Earth.

The chemical basis of hereditary and genetic variation
are related to DNA.

DNA directs the synthesis of RNA which in turn
directs protein synthesis.
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RNA
RNA
The nucleotides within
contain the
base uracil instead of thymine
In the 2’ position, a Hydroxyl grou
(Not present in the 2’ position in Deoxyribose)
Each nucleotide in RNA contains:
a five carbon sugar (ribose)
a phosphate group
a nitrogenous base (all the same ones as DNA, except the
Pyrimidine thymine is replaced with uracil.)
Uracil is a
pyrimidine, as
you can see
from the
structure
Differences with DNA
The RNA

Three major classes of RNA: messenger (mRNA),
transfer (tRNA) and ribosomal (rRNA). Minor classes
of RNA include small nuclear RNA ; small nucleolar
RNA;………..
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The RNA
-
The concentration of
purine and pyrimidine
bases do not necessarily
equal one another in RNA
because RNA is single
stranded. However, the
single strand of RNA is
capable of folding back
on itself like a hairpin and
acquiring double strand
structure.
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RNA is also a nucleic acid 
different sugar 
U instead of T 
Single strand, usually 
Nitrogenous base
(A, G, C, or U)
Phosphate
group
Uracil (U)
Sugar
(ribose)
Figure 10.2C,
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Messenger RNA

mRNA molecules represent
transcripts of structural genes
that encode all the information
necessary for the synthesis of
a single type polypeptide of
protein.

mRNA; intermediate carrier
of genetic information; deliver
genetic information to the
cytoplasm where protein
synthesis take place.

The mRNA also contains
regions that are not translated:
in eukaryotes this includes the
5' untranslated region, 3'
untranslated region, 5' capand
poly-A tail.
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Transfer RNA(tRNA)


All tRNAs share a
common secondary
structure represented by
a cloverleaf. They have
four-paired stems
defining three stem loops
(the D loop, anticodon
loop, and T loop) and the
acceptor stem to which
amino acids are added in
the charging step.
RNA molecules that carry
amino acids to the
growing polypeptide.
a. Function
1) Carries amino acids to mRNA
at the ribosome
2) tRNA molecules are specific
to the amino acid they carry; therefore,
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there are 20 tRNA molecules
Ribosomal RNA (rRNA)
Ribosomal RNA (rRNA) is the central component of
the ribosome, the function of the rRNA is to provide a
mechanism for decoding mRNA into amino acids and to
interact with the tRNAs during translation by providing
peptidyl transferase activity.
a. Important structural component of ribosome 
b. Ribosome - composed of one large and one
small subunit; location for protein synthesis in cells
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Thank You
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