Gene Mutations and DNA Repair

Chapter 18: Gene Mutations and DNA Repair

Types of Mutations

• Induced Mutations: Caused by environmental factors.
• Spontaneous Mutations: Occur naturally due to errors in DNA replication or other internal processes.

DNA Repair Mechanisms

1. Mismatch Repair: Corrects errors missed by DNA polymerase during replication.
2. Direct Repair: Restores modified nucleotides back to original structure.
3. Base-Excision Repair: Removes damaged bases and replaces them with the correct nucleotide.
4. Nucleotide-Excision Repair: Removes larger segments of damaged DNA.

Definition of Mutation

• Mutation: A heritable change in genetic information that can alter protein function, depending on the change's nature and location.

Importance of Mutations

• Evolution: Serve as a source of genetic variation.
• Disease: Cause various genetic disorders and diseases.
• Research: Assist in the study of gene functions through disruptions in biological processes.

Categories of Mutations

Somatic Mutations

• Occur in body cells (non-reproductive).
• Effect is variable; early mutations affect more cells significantly.

Germ-Line Mutations

• Occur in gametes, affecting future generations (50% offspring inherit).

Types of Gene Mutations

1. Base Substitution: Change in one DNA nucleotide.
   • Transition: Purine replaces a purine or a pyrimidine replaces a pyrimidine.
   • Transversion: Purine replaces a pyrimidine or vice versa.
2. Base Deletion or Insertion (Indel): Changes reading frame, causing frameshift mutations.
   • Frameshift mutation example:
     • Wild-type: $AUG hickspace ACA hickspace CGG hickspace AGU hickspace AGA hickspace UAU hickspace UAA$ (Met-Thr-Arg-Ser-Arg-Tyr-Stop)
     • After deletion: $AUG hickspace AAC hickspace GGA hickspace GUA hickspace GAU hickspace AUU hickspace AA$ (Met-Asn-Gly-Val-Asp-Ile)

Phenotypic Effects of Mutations

1. Missense Mutation: Alters one amino acid in a protein.
2. Nonsense Mutation: Creates a premature stop codon.
3. Silent Mutation: Results in no change to amino acid sequence due to redundancy.
4. Neutral Mutation: A missense mutation that does not affect protein function.

Mechanisms of Mutation

• Spontaneous Mutations: Results from errors in DNA replication, chemical changes, etc.

  • Mispairing leads to permanent base substitutions.
  • Strand Slippage causes insertions/deletions.
  • Unequal Crossing Over can lead to duplications or deletions.
  • Chemical Changes: Includes depurination and deamination.

• Induced Mutations: Caused by environmental agents like chemical mutagens and radiation.

  • Alkylating Agents: Add alkyl groups to DNA bases.
  • Ionizing Radiation: Can cause DNA strand breaks.
  • Ultraviolet Light (UV): Can induce covalent bonding among adjacent bases.

DNA Repair Pathways

1. Mismatch Repair: Targets mismatches that DNA polymerase failed to correct during replication.
2. Direct Repair: Specific enzymatic restoration of altered nucleotides.
3. Base Excision Repair: Specialized repair involving removal of damaged bases.
4. Nucleotide Excision Repair: Removes bulky adducts or extensive damages.
5. Repair of Double-Strand Breaks:
   • Homology Directed Repair: Utilizes homologous sequences for accurate repair.
   • Non-Homologous End Joining: Joins broken ends without homologous templates.

Genetic Diseases Associated with DNA Repair Defects

Summary Points

• Ensure to understand mutation types, mechanisms, and repair pathways, as they form the basis for both genetics and medical applications.