DNA is a molecule that carries Genetic
information from generation to next.
Also called as Reserve Bank Of Genetic
Central Dogma of life: Flow of information
from DNA to RNA to Protein synthesis.
Double ring PURINES
Single ring PYRIMIDINES
T or C
A or G
Adenine must pair with Thymine
Guanine must pair with Cytosine
The bases form weak hydrogen bonds
One strand of DNA
goes from 5’ to 3’
The other strand is
opposite in direction
going 3’ to 5’ (sugars)
Semi conservative Model of
Idea presented by Watson & Crick
The two strands of the parental molecule
separate, and each acts as a template for a
new complementary strand
New DNA consists of 1 PARENTAL
(original) and 1 NEW strand of DNA
Begins at site called as "Origins of Replication"
Specific Protein Called as dna A binds to this
site causing double strands to separate.
As the 2 DNA strands open at the origin,
Replication Bubbles form
Prokaryotes (bacteria) have a single bubble
Eukaryotic chromosomes have MANY bubbles
Two strands open forming Replication Forks (Y-
New strands grow at the forks
Parental DNA Molecule
Enzyme DNA Helicase unwinds
and separates the 2 DNA
strands by breaking the weak
Single-Strand Binding Proteins
(SSBP) attach and keep the 2
DNA strands separated and
Before new DNA strands can form,
there must be RNA primers present to
start the addition of new nucleotides
Primase is the enzyme that synthesizes
the RNA Primer
DNA polymerase 3 can then add the
new nucleotides and forms new strand.
DNA polymerase can only add
nucleotides to the 3’ end of the DNA
This causes the NEW strand to be built
in a 5’ to 3’ direction.
DNA polymerase also checks for
incoming nucleotides and act as proof
Synthesis of the New DNA
Leading strand synthesized 5’ to 3’ in the
direction of the replication fork movement.
It is continuous
Requires a single RNA primer
Lagging strand synthesized 5’ to 3’ in the
Discontinuous (i.e., not continuous)
Requires many RNA primers , DNA is
synthesized in short fragments.
Supercoiled DNA relaxed by gyrase & unwound by helicase + proteins:
RNA primer replaced by polymerase I
& gap is sealed by ligase
DNA polymerase 1 removes the RNA primer
The gap left behind is Sealed by Ligase and
new Daughter DNA is formed.
Thus process of replication is ended.
The process of replication is extremely
accurate but errors occurs sometime and
cells posses capacity to repair these errors.
Damaged DNA must be repaired
If the damage is passed on to subsequent
generations, then we use the evolutionary
term - mutation.
Damage from where?
Consequences of DNA replication errors
Chemical agents acting on the DNA
UV light imparting energy into DNA molecule
Spontaneous changes to the DNA
a) Base-excision repair
Presence of the Uracil ,hypoxanthine and
xanthine in DNA is a great example base-
N-glycosylase enzyme replace just the
snip out the defective base
2cut the DNA strand
Add fresh nucleotide via DNA Polymerase.
Gap is sealed by LIGASE
UV light and Ionization radiation causes modification
of bases, strand breaks, cross-linkage, etc.
It recognizes more varieties of damage in DNA .
Cutting of the defective piece by Exinuclease and its
Resynthesis of the cut part by DNA polymerase and
Defect in this mechanism leads to Xeroderma
c) Mismatch repair
These are normally caused by mismatched bases
i.e. AG and CT.
Special enzymes scan the DNA for bulky alterations
in the DNA double helix.
GATC endonuclease cuts the strand and the strand
is digested by Exonuclease.
These gaps are excised and the DNA repaired by
ligase and polymerase enzyme respectively.
Defect in this mechanism causes Lynch syndrome
i.e. patient are of high risk of developing Colon
d) Double-strand break repair
High energy radiation and free radicals
causes DNA breakage and leads to cell
Repair mechanism is of 2 type
1) Non-homologous end joining(Yeast)
2) Homologous end joining (mamals)
Defect: Cancer and Immunodeficiency