Gene Mutations and DNA Repair

Chapter 18: Gene Mutations and DNA Repair

1. Types of Mutations
  • Induced Mutations: Result from environmental factors (mutagens)
  • Spontaneous Mutations: Occur naturally due to errors during DNA replication or cellular processes
2. DNA Repair Mechanisms
  • Mismatch Repair: Detects and replaces incorrect base pairs post-replication.
  • Direct Repair: Corrects specific DNA alterations without removing the base.
  • Base-Excision Repair: Involves the removal of damaged bases and replacement.
  • Nucleotide-Excision Repair: Removes bulky DNA damage that distorts the DNA double helix.
3. Importance of Mutations
  • Evolution: Source of genetic variation, enabling adaptation in natural populations.
  • Diseases: Can lead to genetic disorders and diseases.
  • Genetic Research: Disruptive mutations help understand gene functions.
4. Categories of Mutations
  • Somatic Mutations: Change occurring in non-germline cells, affecting only the individual.
  • Germ-line Mutations: Occur in reproductive cells, passed to offspring, potentially affecting every cell in future generations.
  • Gene Mutations: Small-scale changes affecting a single gene (e.g., point mutations).
  • Chromosomal Mutations: Large-scale changes affecting chromosomal structure or number (e.g., aneuploidies).
5. Types of Gene Mutations
  • Base Substitution: Changes a single nucleotide.
    • Transition: Purine replaces a purine or pyrimidine replaces a pyrimidine.
    • Transversion: Purine replaces a pyrimidine or vice versa.
  • Base Insertion/Deletion (Indel): Alters the reading frame, potentially creating a frameshift mutation.
    • Frameshift Mutation: Disrupts the reading frame of mRNA produced from the gene.
6. Phenotypic Effects of Mutations
  • Missense Mutation: Changes one amino acid in the protein.
  • Nonsense Mutation: Introduces a premature stop codon, leading to truncated proteins.
  • Silent Mutation: No change in amino acid due to redundancy in the genetic code.
  • Neutral Mutation: Changes an amino acid to one that is similar, causing little or no effect on protein function.
7. Mechanisms Causing Mutations
  • Spontaneous Mutations: Resulting from errors during DNA replication, including:
    • Mispairing
    • Strand slippage
    • Unequal crossing over
    • Chemical changes (e.g., depurination, deamination)
  • Induced Mutations: Caused by environmental factors like:
    • Chemical mutagens (e.g., alkylating agents)
    • Radiation (e.g., UV light, ionizing radiation)
8. DNA Repair Mechanisms Explained
  • Mismatch Repair:
    • Detects mismatches based on strand methylation patterns (in bacteria) or recognizes nicks (in eukaryotes).
    • Removes incorrect nucleotide and replaces it with the correct base.
  • Direct Repair: Enzymes like methyltransferases restore the original base structure.
  • Base-Excision Repair: Involves:
    • Recognition and removal of damaged bases by DNA glycosylase.
    • Filling the gap by DNA polymerase and sealing with DNA ligase.
  • Nucleotide-Excision Repair: Removes sections of distorted DNA and replaces with synthesized DNA.
  • Repair of Double-Strand Breaks:
    • Homology-Directed Repair: Uses homologous DNA sequences for accurate repair.
    • Non-Homologous End Joining: Joins broken ends without a template, potentially introducing errors.
9. Genetic Diseases Associated with DNA Repair Defects
  • Xeroderma Pigmentosum: Defects in nucleotide-excision repair; sunlight sensitivity.
  • Cockayne Syndrome: Premature aging and sensitivity to sunlight; defects in nucleotide-excision repair.
  • Li-Fraumeni Syndrome: Cancer predisposition; defects in DNA damage response.
  • Werner Syndrome: Premature aging; homologous recombination defect.
10. Homework Problems - Recommended Exercises
  • Suggested problems for further practice: 1, 2, 3, 5, 6, 7, 15, 19, 23, 26, 28, 29, 44, 45*, 47, 48.