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From Gene to Protein: Translation & Mutations

From Gene to Protein: Translation & Mutations. Chapter 17. Recall:. Central dogma of molecular biology DNA RNA  Protein Steps of gene expression Transcription, RNA processing (eukaryotes), Translation . Translation. Components necessary: tRNA Ribosome

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From Gene to Protein: Translation & Mutations

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  1. From Gene to Protein:Translation & Mutations Chapter 17

  2. Recall: • Central dogma of molecular biology • DNA RNA  Protein • Steps of gene expression • Transcription, RNA processing (eukaryotes), Translation

  3. Translation • Components necessary: • tRNA • Ribosome • Made of RNA and protein subunits • Larger in eukaryotes • Anatomy: • P site – holds tRNA carrying growing peptide • A site – holds tRNA carrying next a.a. in chain • E site – exit site for discharged tRNA

  4. Prokaryotes vs. Eukaryotes • Transcription and translation coupled in prokaryotes • Happen simultaneously • DNA is already in cytoplasm • Transcription and translation are separate in eukaryotes • DNA is in nucleus, ribosomes in cytoplasm • mRNA must be edited first

  5. Translation: Initiation • mRNA binds to the ribosoma • Initiator tRNA binds to start codon on mRNA (AUG) • 1st a.a. = methionine • Large ribosomal subunit binds to complex

  6. Translation: Elongation • tRNAs bring in appropriate amino acid to growing chain based on mRNA codon • This process continues until a stop codon is reached (UGA, UAA, UAG)

  7. Translation: Termination • Peptide synthesis continues until a stop codon is reached • Peptide is released • Where peptide goes depends on its role

  8. The Genetic Code • Made of 3 letter codes: codons (found on mRNA) • Table is used to determine which amino acid each codon codes for • It is the same in almost all organisms • Redundant: more than one codon for some AA’s

  9. Transcription & Translation Summary

  10. When Protein Synthesis Goes Wrong: Gene Mutations • Changes to the DNA sequence resulting in production of malfunctioning or nonfunctioning protein. • Differ from chromosomal mutations since only single nucleotides are affected.

  11. Types of Gene Mutations • Substitution: wrong nucleotide in place • Silent – doesn’t change amino acid, protein • Missense – changes amino acid, protein • Nonsense – changes amino acid to stop codon • Insertion or deletion: nucleotide added or removed • Frameshift

  12. Substitution: Sickle Cell Anemia • Caused by a single nucleotide substitution in one of the polypeptides that makes up hemoglobin (Hgb) • Hgb folds incorrectly, causing RBC’s to become sickle shaped • They cannot carry O2 as effectively

  13. Deletion: Cystic Fibrosis • Most common mutation that causes CF is the result of a deletion in CFTR gene • Mutation causes faulty CFTR protein • This protein transports Cl- ions across cell membrane • Causes mucus buildup in lungs, digestive tract

  14. Insertion: Huntington’s Disease • Caused by a CAG repeat • Normal Huntington gene: 10-26 repeats • Mutant gene: >27 repeats • Autosomal dominant • Causes nervous system degeneration leading to loss of motor function, dementia

  15. Causes of Mutations • Mutagens: physical or chemical agents that cause mutations by • Acting like a normal nucleotide • Causing DNA to be miscopied • Causing the cell to produce chemicals that have mutagenic potential--peroxides

  16. Not all mutations are harmful… • Increase variation, drives evolution • Example: • Mutation in gene CCR5 (important in immune function) • Caused by a deletion causes HIV resistance in homozygotes; delayed onset of HIV infection in heterozygotes • Currently a research study being conducted to genetically modify T-cells so that they have this mutation

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