PHRD5025 Lecture 15 - Regulation of Gene Transcription and Translation

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PHRD5025 Lecture 15 - Regulation of Gene Transcription and Translation
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2013-11-18 02:41:35
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Regulation Gene Transcription Translation
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Regulation of Gene Transcription and Translation
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  1. RNA polymerase holoenzyme
    • Pol subunits + sigma factor
    • requires transcription factors to efficiently initiate transcription
    • binds core promoter sequence & unwindes 17bp of duplex DNA near +1 transcription initiation site
  2. 3 classes of proteins involved in eukaryotic transcriptional activation
    • 1) RNA Pol II recruiting transcription factors
    • 2) enhancer binding transcription factors
    • 3) co-activator proteins
  3. optimal binding sequence for a specific DNA binding protein
    consensus sequence
  4. where more TFs recognize specific sequences
    within the major groove of the DNA duplex
  5. 1 minor groove binding protein mentioned in this lecture
    TATA-binding protein (TBP)
  6. 3 extracellular signals that can regulat TFs
    • 1) phosphorylation (eg: c-Myc)
    • 2) release from an inhibitory complex (eg: NFkB-IkB)
    • 3) ligand activation (eg: steroid hormones)
  7. protein activation by mitogenic signals via phosphorylation, regulates cell proliferation genes
    c-Myc
  8. nucleosome
    histones + DNA
  9. 2 enzymes that play a major role in chromatin remodeling by regulating lysine acetylation
    histone acetyltransferases (HATs) & histone deacetylases (HDACs)
  10. 3 steps of post-transcriptional processing of eukaryotic mRNA primary transcript
    • 1) 5' capping
    • 2) splicing
    • 3) 3' polyadenylation
  11. 2 roles of 5' cap structure
    • 1) mRNA transport to cytoplasm
    • 2) translational efficiency (directs binding of ribosome to mRNA)
  12. structure that carries out splicing out of introns to form mature mRNA
    spliceosome
  13. 2 roles of poly-A tail
    • 1) mRNA stability
    • 2) translational efficiency
  14. restricts access of RNA pol to promoters
    chromatin
  15. direction in which proteins are synthesized
    from amino terminus toward carboxy terminus
  16. 5 main stages of protein synthesis
    • 1) activation of amino acids
    • 2) initiation
    • 3) elongation
    • 4) termination and release
    • 5) post-translational processing
  17. approximate size of ribosomes
    ~2700kDa
  18. aminoacyl-tRNA synthetases
    attach amino acid to tRNA to form aminoacyl-tRNA
  19. how many tRNA's are there for Met?
    2
  20. purine-rich sequence after the first AUG that defines the initiation codon
    Shine-Delgarno Sequence

    complementary to region of 16s rRNA
  21. 3 steps of prokaryotic initiation
    • 1) IF-3 binds small subunit, IF-1 binds A-site; 30S subunit moves to SD seq & positions P-site at AUG
    • 2) IF-2/GTP/fMet-tRNA complex binds start codon at P-site
    • 3) large subunit binds & initiation factors released upon GTP hydrolysis
  22. is there a Shine-Delgarno sequence in eukaryotic mRNAs?
    NO
  23. 3 steps of prokaryotic elongation
    • 1) binding of incoming aminoacyl-tRNA
    • 2) peptide bond formation
    • 3) translocation
  24. protein that delivers complementary anticodon to A-site
    elongation factor Tu (EF-Tu)
  25. - ribozyme that catalyzes the formation of the peptide bond
    - component of large 50S ribosomal subunit
    peptidyl transferase
  26. protein using GTP and is required for translocation
    EF-G (or translocase)
  27. EF-Tu and EF-G eukaryotic analogs
    eEF1 and eEF2
  28. purpose of proof-reading at the ribosome
    for correct codon-anticodon recognition
  29. # releasing factors in prokaryotes vs eukaryotes
    3 vs 1
  30. Ricin MOA
    inactivates 60S subunit by depurination of 23S rRNA
  31. BCR-ABL tyrosine kinase inhibitor
    Gleevec (imatinib mesylate)
  32. EGF RTK inhibitors (2)
    • Iressa (gefitinib)
    • Tarceva (erlotinib)

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