Genetics: Mutation Types and DNA Repair

Mutation

• A mutation is a permanent change in the base sequence of DNA.
• Mutations can be neutral, beneficial, or harmful.
• Mutagens are substances or energy sources that induce mutations.
• Spontaneous mutations occur in the absence of mutagens.
• Mutations may involve a single base change or large-scale chromosomal abnormalities.
• New alleles arise due to mutations.
• Most genetic mutations are neutral or harmful.

Types of Mutations

• Base substitution (point mutation): A change in one base in DNA.
  • Missense mutation: A base substitution that results in a change in the corresponding amino acid.
  • Nonsense mutation: A base substitution that results in a nonsense (stop) codon.
  • Silent mutation: A base substitution that does not result in a change in the amino acid.
• Frameshift mutation: An insertion or deletion of one or more nucleotide pairs, causing a shift in the reading frame during translation.

DNA Repair

• DNA repair is a three-step process:
  • Recognition: Repair proteins detect and tag damaged DNA.
  • Removal: Repair enzymes remove the damaged segment.
  • Replacement: A repair DNA polymerase fills the gap with the correct sequence of bases.
• Each step employs different repair proteins and specialized enzymes.
• Damaged DNA is removed and replaced.

DNA Damage and Diseases

• Failure to repair DNA damage can lead to serious diseases like cancer.
• UV radiation can cause thymine dimers.
• Ionizing radiation, such as X-rays and gamma rays, causes the formation of ions that can oxidize nucleotides and break the deoxyribose-phosphate backbone.
• Xeroderma pigmentosum (XP) is a condition where people lack the functional versions of repair proteins, and they accumulate mutations leading to skin cancer.

Mutations Affecting Protein Function

• Even single-base changes can alter protein function enough to produce a harmful phenotype (e.g., a disease).
• Frameshift mutations alter protein structure extensively, typically destroying its normal function and causing severe phenotypes.
• Silent mutations have no impact on the protein structure or phenotype.
• Rare mutations can be beneficial, improving protein efficiency or functionality.

Operon Model of Gene Expression

• Promoter: A DNA segment where RNA polymerase initiates transcription.
• Operator: A DNA segment that controls the transcription of structural genes.
• Operon: A set of operator and promoter sites and the structural genes.
• Inducible Operon: Structural genes are not transcribed unless an inducer is present.
• Repressible Operon: Structural genes are transcribed until they are turned off.

lac Operon

• Regulation of the lac operon:
  • In the absence of lactose, a repressor binds to the operator, preventing transcription.
  • In the presence of lactose, allolactose (an inducer) binds to the repressor, preventing it from binding to the operator, allowing transcription to occur.

lac Operon- Positive Regulation

• Catabolite repression: Cells preferentially use glucose; cAMP builds in the absence of glucose.
• In the absence of glucose, cAMP binds to CAP (catabolic activator protein), which then binds to the promoter of the lac operon.
• Activating lac transcription.

Repressible Operon (Tryptophan Operon)

• Structural genes are transcribed until excess tryptophan is available.
• Tryptophan acts as a corepressor by binding to the repressor protein and activating it, allowing it to bind to the operator and prevent further transcription.

Post-transcriptional Control

• Riboswitches: mRNA molecules that bind to substrates to change their structure.
• microRNAs (miRNAs): Base pair with mRNA, causing it to become double-stranded and leading to degradation. Preventing protein synthesis.
• Epigenetics: Methylation of nucleotides turn genes off, and methylation patterns may be inherited.

Gene Expression Regulation

• Tight packing of DNA makes genes transcriptionally inactive.
• Regulation of transcription conserves cellular resources.
• mRNA is degraded to avoid protein synthesis.
• Translation is regulated to keep mRNA ready.
• Proteins are directly regulated after synthesis.