DNA Damage and Repair.pptx

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

7. 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

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

9. 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.

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

11. 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).

12. Figure 19.13: Dimer of two thymine bases.

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

14. 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 .

15. 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.

16. 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

17. ‰ 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

18. 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.

19. MECHANISMS OF DNA REPAIR