This presentation is about DNA Damage and DNA Repair

1. DNA
Damage

2. The types of damage inflicted on
the DNA molecule by various
physical and chemical agents
(mutagens) are broadly classified
into four categories
DNA DAMAGE

3. TYPES OF DNA DAMAGE

4. DNA Repair
Mechanism

5. The mechanisms used for the repair of DNA involve:
 First recognition of distorted region of the DNA.
 Secondly removal or excision of the damaged region of
the DNA strands.
 Then filling of gap left by the excision of the damaged
DNA by DNA polymerase.
 Finally sealing the nick in the strand that has undergone
repair by a ligase

6. Types of DNA Repair Systems
 Mismatch repair
 Base excision repair
 Nucleotide excision repair
 Direct repair
 Homologous recombination and Non-homologous
end-joining repair

8. ● Even though replication occurs with
high fidelity, defects do occur during
copying. Mismatch repair corrects
errors involving single base pair or a
small region of unpaired DNA
MISMATCH REPAIR

9. Figure 19.11: A methyl directed mismatch repair mechanism.

11. Base Excision Repair (BER)
The bases of DNA can be altered, either
spontaneously or by the action of deamination or
alkylating compounds.
Lesions involving base alterations or loss can be
corrected by base excision repair mechanism.

12. Figure 19.12: Base excision repair pathway. Uracil base formed by
the deamination of cytosine is excised and replaced by cytosine.

14. Nucleotide Excision Repair (NER)
 In nucleotide excision (Latin exci = to cut out) repair,
enzyme excinuclease hydrolyzes two phosphodiester
bonds one on either side of the distortion caused by the
lesion.
 One of the best understood examples of nucleotide
excision repair is excision of a pyrimidine dimer.
 Three enzymatic activities are essential for this repair,
UvrA, UvrB, UvrC (UvrABC).

15. Figure 19.13: Dimer of two thymine bases.

17. Figure 19.14: Nucleotide excision repair mechanism
containing a thymine dimer.

18. Direct Repair Pathway (DR)
Several types of damage are repaired without removing
a base or nucleotide.
An example of direct repair is the
photochemical cleavage of pyrimidine dimers.

19. Homologous Recombination (HR)and Non-homologous
End-joining Repair (NHEJ)
This repair mechanisms used to repair DNA double
strand breaks in eukaryotic cells.
The choice between the two depends on the phase of the
cell cycle and the exact type of double strand breaks to
be repaired.

20. During G0/G1 phases of the cell cycle,
DNA double strand breaks are corrected
by the non-homologous end-joining repair
mechanism, whereas during S, G2, and M
phases of the cell cycle homologous
recombination is utilized

21. • ‰
Xeroderma pigmentosum (XP): Defective nucleotide excision
repair (NER) mechanism; sensitivity to UV light; skin cancers.
• ‰
Ataxia telangiectasia (AT): Defective ATM gene; sensitivity to UV
light; lymphoreticular neoplasms.
• Fanconi anemia: Defective genes are in chromosomes 20q and
9q. Defect in DNA cross-link repair; increased occurrence of cancer.
Diseases Associated with DNA Repair Mechanisms

22. • Bloom’s syndrome: Gene is in 15q. Defect is in DNA ligase or
helicase; lymphoreticular malignancies.
• Cockayne syndrome: Defect in NER mechanism; transcription
factor II H is defective; stunted growth and mental retardation.
• Hereditary polyposis colon cancer (Lynch syndrome): Defective
gene in chromosome 2. Defect in hMSH 1 and 2 genes;
mismatch repair is defective.

23. MECHANISMS OF DNA REPAIR