Biology Chapter on Lac Operon Regulation

Negative Regulation by Lac Repressor

• In the absence of lactose, the lac repressor binds to the operator (O site), blocking RNA polymerase access to structural genes.
• This binding results in no transcription or translation.

Positive Control by Induction in the Presence of Lactose

• Permease facilitates the transport of lactose across the cell membrane.
• β-galactosidase hydrolyzes lactose into glucose and galactose.
• Allolactose, formed from glucose and galactose, functions as an inducer by binding to the repressor protein.
• When allolactose binds, the repressor undergoes a conformational change, preventing it from binding to the O site, allowing transcription of structural genes.
• CAP-binding protein enhances transcription in the absence of glucose.

Transcription Regulation Mechanism

• Transcription begins at the 5' untranslated region (5' UTR) of mRNA.
• Ribosome attaches to the Shine-Dalgarno sequence within the 5' UTR, initiating translation of the leader peptide.
• High histidine levels allow for normal ribosome function, while low levels lead to ribosome stalling.
• When stalled, RNA polymerase continues transcription of structural genes.

Mechanism of Gene Expression Regulation in Eukaryotes

• Eukaryotic DNA is associated with histones, preventing the transcriptional machinery from accessing promoters.
• Key mechanisms include chromatin remodeling, histone modification, DNA methylation, gene amplification, and gene deletions.

Chromatin Remodeling

• Involves the displacement of nucleosomes from DNA sequences to activate genes, powered by ATP.

Covalent Modification of Histone Tails

• Acetylation by histone acetyltransferases (HATs) adds acetyl groups, reducing the interaction between histones and DNA, thus promoting transcription.

Mutation Types

• Mutations are heritable changes in DNA sequence and can be small (affecting one or two nucleotides) or large (affecting whole chromosomes).
• Loss of function mutations eliminate gene product function (null mutations); gain of function mutations confer new functions (dominant alleles).

Classification Based on Molecular Change

• Point Mutations: Changes in a single nucleotide.
  • Silent Mutations: No change in protein.
  • Missense Mutations: Change one amino acid in the protein.
  • Nonsense Mutations: Create a stop codon, leading to truncated proteins.

Examples of Diseases Caused by Point Mutations

• Sickle Cell Anemia: Affects red blood cell shape, causing severe pain and infections, a single gene disorder.
• Rett Syndrome: Mainly impacts girls; associated with mutations in the MECP2 gene causing learning and coordination difficulties.

Insertions and Deletions (Indels)

• Indels occur when base pairs are added or removed, affecting downstream translation.
• Frameshift mutations result from indels that aren't multiples of three, leading to altered protein function.

Specific Mutation Effects on Proteins

• Hemoglobin Wayne: Results from a frameshift mutation near a standard termination codon.
• Huntington Disease: Caused by CAG repeat expansions in the HD gene on chromosome 4, with onset dependent on repeat number.
• Fragile X Syndrome: Involves CGG repeats in the FMR-1 gene, excess repeats lead to intellectual disabilities.
• Myotonic Dystrophy: Caused by CTG repeat in the MDPK gene; repeat numbers correlate with disease severity.

Types of Mutations

• Spontaneous Mutations: Occur naturally due to replication errors or internal factors.
• Induced Mutations: Result from external factors like radiation or chemicals.

Sources of Spontaneous Mutations

• Often arise from replication errors that go undetected, with tautomerism of bases contributing to inaccuracies.