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1. Vikas Kumar
A0999320037

2. What is DNA Damage
DNA damage is the alteration in the chemical structure of DNA,
such as a break in a strand of DNA, a base missing from the
backbone of DNA, a chemically changed base.
The genetic information encoded in the DNA must remain
uncorrupted.
Any chemical changes must be corrected.
A failure to repair DNA produces a mutation.

3. Sources of Damage DNA
Endogenous damage
 It includes damage from within the cell.
 It also includes replication errors.
Example: Attack by reactive oxygen species produced
from normal metabolic byproducts
Exogenous damage
 It includes damage caused by external agents
Examples: 1.UV, X rays and gamma rays.
2.Plants of comfrey species.
3.Viruses.

4. Causes of DNA Damage
 UV Rays
 Random photons of ultraviolet light induce aberrant bonding between
neighboring pyrimidines(thymine and cytosine) bases on the same strand of
DNA.
 This will prevent the replication.

5.  Alkylating agents
 Methyl and ethyl group added to DNA bases alters
the structure of DNA.
Deamination
 An amino group of cytosine is removed, and the base becomes uracil.
 An amino group of adenine or guanine is removed, and the base becomes hypoxanthine.

6. Consequences of DNA Damage
 Leads to genome instability.
 Increased cancer risk.
 Accelerated ageing.
 Neurodegenerative diseases.

7.  DNA repair refers to the number of processes by which a cell identifies and
corrects damage to the DNA molecules that encode its genome.
 Depending on the type of damage inflicted on DNA’s double helical structure, a
variety of repair strategies have evolved to restore lost information
DNA Repair

8. TYPES OF DNA REPAIR MECHANISMS
1. Direct reversal
2. Excision repair
a) Base excision repair
b)Nucleotide excision repair
3. Mismatch repair
4. Recombinational repair

9. Direct Repair
 This system act directly on damaged nucleotides and convert each one back to its
original structure.
 But only a few damaged nucleotides can be repaired directly.
 Pyrimidine dimers are repaired by a light-dependent direct system called
photoreactivation.
 O6-methylguanine-DNA methyltransferase I and II (MGMT), also called DNA alkyl
transferases, remove the modified bases like O6-alkylguanine and O4-alkylthymine.
 The photolyase protein is not found in all living cells. However, the DNA alkyl
transferases are widespread in nature.

11. Excision Repair
 It involves excision of a segment of the polynucleotide containing
a damage site, followed by resynthesis of the correct nucleotide
sequence by a DNA polymerase.
 Excision → Resynthesis → Ligation.
 Excision repair is of two types:
a)Base excision repair
b) Nucleotide excision repair

12. Base Excision Repair
• BER repairs damage to a single base caused
by oxidation, alkylation, hydrolysis, or
deamination.
• The damaged base is removed by a DNA
glycosylase, resynthesized by a DNA
polymerase, and a DNA ligase performs the
final nick- sealing step.

13. Nucleotide Excision Repair
Nucleotide excision repair recognizes bulky helix- distorting lesions such as
pyrimidine dimers and 6,4 photoproducts and treats them.

14. Mismatch repair
 This difference allows the repair
enzymes to identify the strand that
contains the errant nucleotide
which requires replacement.
 If a mismatch or small loop is
found, a GATC endonuclease cuts
the strand bearing the mutation at a
site corresponding to the GATC.
 An exonuclease then digests this
strand from the GATC through the
mutation, thus removing the faulty
DNA.

15. Recombinational Repair
Recombinational repair requires the presence
of an identical or nearly identical sequence
to be used as a template for repair of the
break in the DNA strand.
The enzymatic machinery responsible is
nearly identical to the machinery responsible
for chromosomal crossover during meiosis.