DNA STRUCTURE
NUCLEIC ACIDS
Include
DNA: Deoxyribonucleic acid
RNA: Ribonucleic acid
DNA (Deoxyribonucleic acid):
 Site : Mostly found in the nucleus of cell and small
amount is found in the mitochondria.
 DNA carries all the genetic informations of the
individual
- Nuclear DNA: carries the genetic informations in the
chromosomes that encode functional proteins or
functional RNA.
-
Mitochondrial DNA:
•
contains:
• 1- genes encode proteins of the electron transport chain.
• 2- genes encoding transfer RNA (tRNA) and the small and large
subunits of ribosomal RNA (rRNA).
• DNA must be to replicated precisely each
time the cell divides, in such a way that each
daughter cell acquires the same amount of
genetic material.
 Structure:
• DNA is formed of two chains (strands).
• The 2 strands wind around each other
forming a double helix (Watson and crick
model).
Each strand (chain ) of DNA is formed of nucleotides
• Each nucleotide of DNA is formed of :
1. Sugar (deoxy ribose).
2. Phosphate group.
3. Nitrogen containing bases:
- Purine bases (bases containing 2 rings (Adenine [A], Guanine
[G])
- Pyrimidine bases (bases containing single ring (Thymine [T],
Cytosine)
• Linking of the base to the sugar (at the 1’
carbon of the sugar) is called nucleoside
Figure: β-Glycosidic linkage in a deoxyribonucleoside.
Linking of nucleoside to phosphate group ( at
the 5’ carbon of the sugar) is called nucleotide
• Nucleotides are linked in each DNA strand
through Phosphodiester bond between the
sugars and phosphates
Figure: Formation of a phosphodiester bond between 2 successive nucleotides
Ester bonds are strong covalent bonds formed by the reaction of an acid and alcohol(- OH).
Phosphodiester bond is a group of strong covalent bonds between a phosphate group and two
5-carbon ring carbohydrates (pentoses) over two ester bonds.
Fig.: A polynucleotide chain of DNA
Each DNA strand (chain) has 2 ends:
1. The 5’ end has a free phosphate group.
2. The 3’ end has a free hydroxyl group.
Note the direction of DNA replication is in a 5’ -3’ direction.
• The hydrophilic (polar) deoxyribose phosphate backbone
of each chain is on the outside of the DNA molecule,
whereas the hydrophobic (nonpolar bases) are stacked
inside perpendicular to the axis of the helix.
• The 2 DNA strands wind around each other in antiparallel
manner; that is From any fixed position in the helix, one
strand is oriented in the 5′ 3′ direction and the other in
the 3′ 5′ direction.
• The double helix made by winding of the 2 DNA strands
around each other, is stabilized by hydrogen bonding
between the bases of the 2 strands and by the
hydrophobic interactions between the stacked bases.
• Base pairing rule: Thymine always pair with
adenine and cytosine always pair with guanine.
So one polynucleotide chain is of the double
helix is always complementary to the other.
• Thymine and adenine bases are connected by 2
hydrogen bonds , while cytosine and guanine
are connected by 3 hydrogen bonds. This makes
G-C base pairs more stable than A-T base pairs
• On its exterior surface, the double helix of DNA contains
two deep grooves between the ribose-phosphate chains.
These two grooves are of unequal size and termed the
major and minor grooves. The difference in their size is
due to the asymmetry of the deoxyribose rings and the
structurally distinct nature of the upper surface of a basepair relative to the bottom surface.
•
• Polymorphism of DNA
• Polymorphism of DNA
Parameters
A -DNA
B-DNA
Z-DNA
Direction of helical rotation
Right
Right
Left
Residues per turn of helix
11
10
12 base pairs
Rotation of helix per residue (in degrees)
33
36
-30
Base tilt relative to helix axis (in degrees)
20
6
7
Major groove
narrow and deepwide and deep
Flat
Minor groove
wide and
shallow
narrow and deep
narrow and deep
Orientation of
N-glycosidic Bond
Anti
Anti
Anti for Pyrimidine, Syn for
Purine
Comments
most prevalent within occurs in stretches of
cells
alternating purine-pyrimidine
base pairs
DNA organization
In humans, each cell contains 46 chromosomes whose total
length equals one meter .
So, chromosomes must be condensed into chromatin to fit into
the nucleus.
The chromatin in eukaryotic cells consists of:
Nuclear DNA
bound to
Histones proteins
&
smaller amounts of non histone proteins
(Enzymes involved in DNA replication and
transcription)
&
Small amount of RNA
(snRNA)
The chromatin in eukaryotic cells consists of:
Nuclear DNA
bound to
Histones proteins
&
smaller amounts of non histone proteins
(Enzymes involved in DNA replication and
transcription)
&
Small amount of RNA
(snRNA)
HISTONES
-Are basic proteins (having positive charges), so
they form ionic bonds with the negatively charged
DNA so their binding is facilitated.
• - 5 types: H1, H2A, H2B, H3, H4.
• - Functions:
• They help condensation of the DNA into more
compact chromosomes.
• Protect the DNA from digestion by exonucleases.
• Modified histones: Has an important role in
changing the structure of chromatin and
chromatin function e.g. acetylation of H3 and H4
is associated with activation or inactivation of
gene expression.
Nucleosome structure
Nucleosome consists of
1- DNA core:
Formed of supercoiled DNA surrounding
histone octamer (2 molecules of each of H2A,
H2B, H3, H4).
2- Linking region:
It joins one nucleosome core to the next
Formed of 60 bp of DNA and 1 molecule of
histone (H1) which protects the linker DNA
from digestion by exonucleases
Chromatin is built from
repeating nucleosomes
units
If the chromatin is placed in low salt buffer
and viewed with E/M (i.e If the chromatin
is pulled into a linear strucrure)→→→→ It
resembles a string of beads( with the
beads representing nucleosome cores and
the string representing the DNA linker)
Compaction of chromatin
 Condensation of the nucleosomes with histone H1 in the
centre form the 10 nm fibril which represents 7 fold
shortening of the linear ß- form DNA.
 Supercoiling of the 10 nm fibril with 6-7 nucleosomes per
turn form the 30 nm fiber which represents 50 fold
shortening of the length of DNA.
 Supercoiling of the 30 nm fiber into superloops (700 nm in
diameter).
 Each 6 superloops attached to a protein scaffold form a
rosette.
 Each 30 rosette form one coil.
 Each 10 coils form one chromatid.
Chromosomes
2 identical sister chromatids attached
at the centromere →→ one chromosome
(in the metaphase)
The centromere
- is rich in A=T and is about 130 bp long.
- is connected to specific proteins to form a
complex known as kinetochore which is
connected to mitotic spindle. This complex is
essential structure for chromosomal
segregation during mitosis.