OIA1003 NUCLEIC ACID DISEASE & DRUGS

Mutation

A permanent change in DNA sequence, may or may not alter phenotype.

Spontaneous Mutations

Occur due to replication errors or natural processes (e.g., depurination).

Induced Mutations

Caused by mutagens like chemicals (e.g., ethidium bromide) or radiation.

Point Mutation

A single base substitution in DNA (e.g., Sickle Cell Anemia).

Missense Mutation

Alters one amino acid in the protein (e.g., Sickle Cell → Glu to Val).

Nonsense Mutation

Introduces a premature stop codon, truncating the protein (e.g., DMD).

Frameshift Mutation

Insertion/deletion changes reading frame (e.g., Tay-Sachs Disease).

Splice Site Mutation

Alters mRNA splicing, producing faulty proteins (e.g., Beta-Thalassemia).

Repeat Expansion Mutation

Abnormal expansion of triplet repeats (e.g., Huntington’s Disease).

Chromosomal Mutation

Large structural changes (e.g., Down syndrome = Trisomy 21).

Centromere Function

Ensures chromosome segregation during mitosis and meiosis.

Telomere Function

Protects chromosome ends, prevents loss of genetic material.

Cystic Fibrosis

Mutation in CFTR gene.

Can affect protein production, processing, or function.

CCR5-Δ32 Mutation

Protective against HIV; example of a beneficial mutation.

Werner & Bloom Syndromes

Premature aging syndromes caused by telomere shortening.

Cancer & Telomerase Reactivation

Tumor cells express telomerase, enabling limitless division.

Loss of Function Mutation

Reduced/no protein activity; often recessive.

Gain of Function Mutation

New/abnormal protein function; often dominant.

Neutral Mutation

No effect on organism fitness; passed through genetic drift.

Lethal Mutation

Causes non-viability of the organism.

Telomerase

Ribonucleoprotein enzyme that extends telomeres.

Anti-Telomerase Therapy

Inhibits telomerase in tumor cells, promoting apoptosis.

G-Quadruplex Stabilizers

Stabilize G-rich DNA structures → prevent telomere elongation.

Cisplatin

Cross-links DNA, distorts its structure → blocks replication.

DNA Adduct Formation

Prevents normal DNA transcription/replication in cancer cells.

Rifampicin

Binds β-subunit of bacterial RNA polymerase.

Used in TB, leprosy, Legionnaires’ disease.

Dactinomycin (Actinomycin D)

Intercalates in G-C rich regions, blocks topoisomerase movement.

Used in cancer therapy.

α-Amanitin

Inhibits RNA polymerase II → blocks transcription elongation.

Found in Amanita phalloides (poisonous mushroom).

Puromycin

Binds to A site, causes premature chain termination.

Mimics aminoacyl-tRNA.

Tetracycline

Binds 30S ribosome, blocks tRNA entry.

Chloramphenicol

Binds to 50s subunit & inhibits peptidyl transferase in prokaryotes.

Used for typhoid, meningitis.

Cycloheximide

Inhibits peptidyl transferase in eukaryotes.

Erythromycin

Binds to 50S subunit, blocks translocation of growing peptide.

Streptomycin

Binds 30S subunit, causes misreading of mRNA.

Mutation Testing

Helps in diagnosis & selection of targeted therapy.

Transcription & Translation Inhibitors in Chemotherapy

Used to halt tumor cell proliferation

Selective Toxicity of Inhibitors

Antibiotics target prokaryotic machinery, sparing eukaryotic cells.

Therapeutic Targeting of Gene Expression

Emerging strategies include RNA interference, antisense oligonucleotides.