DNA DAMAGE AND REPAIR MECHANISM (M.sc Botany).pptx

DNA DAMAGE AND REPAIR MECHANISMa

1. DNA DAMAGE AND REPAIR MECHANISM (M.sc Botany) SlideMake.com

2. Introduction to DNA Damage and Repair Mechanism DNA damage can occur due to various factors such as UV radiation, chemical exposure, and errors in DNA replication. Maintaining genomic integrity is crucial for the survival and proper functioning of cells. Cells have evolved intricate mechanisms to detect and repair DNA damage to prevent mutations and maintain genetic stability.

3. Types of DNA Damage DNA damage can manifest as single-strand breaks, double-strand breaks, base modifications, and crosslinks. Each type of damage can lead to different consequences such as mutations, cell death, or genomic instability. Cells have specialized repair pathways to address specific types of DNA damage efficiently.

4. Direct Reversal Repair Mechanism In direct reversal repair, specific enzymes recognize and reverse DNA damage without excising nucleotides. Examples include photolyases that repair UV-induced thymine dimers and alkyltransferases that remove alkyl groups from bases. This mechanism is highly specific and does not involve the removal of damaged nucleotides.

5. Base Excision Repair (BER) BER is a repair pathway that corrects small, non-helix-distorting base lesions. It involves the sequential action of DNA glycosylases, AP endonucleases, DNA polymerases, and ligases. BER is critical for repairing oxidative DNA damage and maintaining genomic stability.

6. Nucleotide Excision Repair (NER) NER is a versatile repair pathway that removes bulky DNA lesions that distort the DNA helix, such as UV-induced thymine dimers. It involves the recognition of damage, incision on both sides of the lesion, DNA synthesis, and ligation. Defects in NER can result in disorders like xeroderma pigmentosum characterized by extreme sensitivity to UV radiation.

7. Mismatch Repair (MMR) MMR corrects base-pairing errors that escape the proofreading function of DNA polymerases during replication. MutS, MutL, and MutH proteins coordinate the recognition and excision of the mismatched nucleotide. MMR is crucial for maintaining the fidelity of DNA replication and preventing mutations.

8. Homologous Recombination (HR) HR is a high-fidelity repair pathway that uses an undamaged homologous DNA template for repair. It is essential for repairing double-strand breaks and stalled replication forks. HR plays a vital role in meiotic recombination and the restart of collapsed replication forks.

9. Non-Homologous End Joining (NHEJ) NHEJ is an error-prone repair pathway that directly ligates broken DNA ends without requiring a homologous template. It is crucial for repairing double-strand breaks in non-dividing cells. NHEJ can lead to small insertions or deletions at the repair site, contributing to genetic diversity.

10. Translesion Synthesis (TLS) TLS is an error-prone DNA damage tolerance mechanism that allows DNA replication to proceed past damaged bases. Specialized DNA polymerases, known as translesion synthesis polymerases, can replicate across lesions but with lower fidelity. TLS is a double-edged sword as it can prevent replication fork stalling but may introduce mutations.

11. Regulation of DNA Damage Response Cells activate DNA damage response pathways to coordinate repair, cell cycle arrest, and apoptosis. Key regulators such as ATM, ATR, and p53 play crucial roles in sensing and signaling DNA damage. Dysregulation of DNA damage response pathways can lead to genomic instability and cancer.

12. Environmental Factors and DNA Damage Environmental factors like UV radiation, ionizing radiation, chemicals, and pollutants can induce DNA damage. Chronic exposure to these factors can overwhelm DNA repair mechanisms and increase the risk of mutations. Understanding how environmental factors impact DNA damage and repair is essential for health and environmental protection.

13. DNA Repair Deficiencies and Human Diseases Inherited mutations in DNA repair genes can lead to various genetic disorders, such as xeroderma pigmentosum and Lynch syndrome. These disorders are characterized by increased susceptibility to cancer due to impaired DNA repair mechanisms. Studying DNA repair deficiencies provides insights into the molecular basis of disease and potential therapeutic targets.

14. Emerging Technologies in DNA Repair Research Advanced technologies like CRISPR-Cas9, single-molecule imaging, and high-throughput sequencing have revolutionized DNA repair research. These tools enable precise genome editing, real-time visualization of repair processes, and comprehensive analysis of DNA damage and repair. Continued innovation in technology will further enhance our understanding of DNA repair mechanisms and their implications.

15. Future Directions in DNA Repair Research Future research aims to uncover novel DNA repair pathways, regulatory mechanisms, and therapeutic targets. Exploring the crosstalk between DNA repair and other cellular processes will provide a comprehensive view of genome maintenance. Harnessing the knowledge of DNA repair mechanisms holds promise for advancing personalized medicine and cancer treatments.

16. Importance of DNA Damage and Repair in Plant Biology DNA damage and repair mechanisms are crucial for maintaining genome stability in plants exposed to environmental stresses. Understanding how plants respond to DNA damage can help improve crop resilience and agricultural productivity. Studying DNA repair in plants provides insights into evolutionary adaptations and genetic diversity in natural populations.

17. Plant-Specific DNA Repair Mechanisms Plants have evolved unique DNA repair mechanisms tailored to their sessile lifestyle and exposure to environmental stressors. Specialized repair pathways, such as photoreactivation and base excision repair, help plants cope with UV damage and oxidative stress. Elucidating plant-specific DNA repair mechanisms offers opportunities for biotechnological applications in crop improvement and stress tolerance.

18. Cross-Kingdom Comparisons of DNA Repair Comparing DNA repair mechanisms across kingdoms reveals both conserved and divergent strategies to maintain genomic integrity. Understanding similarities and differences in DNA repair between plants, animals, and microbes can uncover fundamental principles of genome maintenance. Cross-kingdom comparisons provide a holistic view of evolutionary adaptations and the impact of environmental factors on DNA repair.

19. Educational and Career Opportunities in DNA Repair Research Pursuing advanced studies in DNA repair research offers exciting opportunities to contribute to scientific discoveries and medical advancements. Careers in academia, biotechnology, pharmaceuticals, and healthcare are available for individuals with expertise in DNA damage and repair mechanisms. Continuous learning and professional development in DNA repair research can lead to fulfilling and impactful careers in the field.

20. Collaborative Research in DNA Repair Collaborative research involving multidisciplinary teams enhances the understanding of complex DNA repair processes and their implications. Partnerships between academia, industry, and government institutions drive innovation in DNA repair research and its translation into practical applications. Building collaborative networks and sharing knowledge globally accelerates progress in unraveling the mysteries of DNA damage and repair.

21. Conclusion DNA damage and repair mechanisms are fundamental processes that safeguard genomic integrity and ensure cell survival. Elucidating the intricate pathways of DNA repair offers insights into disease mechanisms, evolutionary adaptations, and environmental responses. Continued research and collaboration in DNA repair hold promise for addressing health challenges, advancing biotechnology, and shaping the future of scientific discovery.

22. References Lindahl T. (1993). Instability and decay of the primary structure of DNA. Nature, 362(6422), 709-715. Hoeijmakers JH. (2009). DNA damage, aging, and cancer. New England Journal of Medicine, 361(15), 1475-1485. Ciccia A., Elledge S. J. (2010). The DNA damage response: making it safe to play with knives. Molecular cell, 40(2), 179-204.