DNA Damage and Repair Mechanisms

Introduction

• Each cell's DNA can be damaged tens of thousands of times daily.
• Human body has approximately 100 trillion cells, leading to a quintillion DNA errors daily.
• DNA provides blueprints for proteins; damage can cause serious issues like cancer.

Types of DNA Errors

• Nucleotide Damage: Building blocks of DNA can be damaged.
• Incorrect Base Pairing: Mismatched nucleotides lead to mutations.
• Strand Nicks: Can interfere with DNA replication or cause DNA sections to mix up.

DNA Repair Mechanisms

Enzymatic Repair

• Specialized enzymes fix various types of damage.

Common Repair Pathways

Base Mismatch Repair

• Mistakes during DNA replication corrected by DNA polymerase.
• Second set of proteins further checks for mismatches.
• Reduces errors to about one in one billion.

Post-Replication Damage

Chemical Changes

• Environmental Exposure: Compounds like those in tobacco smoke.
• Naturally Occurring Molecules: Like hydrogen peroxide.

Specific Repair Mechanisms

Base Excision Repair

• Fixes single-base damage.
• Enzymes remove damaged base and replace nucleotides.

Nucleotide Excision Repair

• Addresses complex damages (e.g., UV light-caused adjacent nucleotide bonding).
• Team of proteins removes and replaces a long strand of nucleotides.

Double Strand Breaks

• Caused by high-frequency radiation (gamma rays, x-rays).
• Homologous Recombination: Uses undamaged DNA as a template.
• Non-Homologous End Joining: Fuses broken ends without a template, less accurate.

Impact of DNA Damage

• Changes can lead to beneficial mutations driving evolution.
• However, most desirable for DNA to remain stable.
• DNA repair defects linked to premature aging and cancer.

Conclusion

• DNA repair processes operate continuously to maintain genetic integrity, performing billions of repairs daily.