05 - Nucleus Structure & Cell Cycle

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280630
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05 - Nucleus Structure & Cell Cycle
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2014-08-22 20:15:37
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nucleus structure nucleolus cell cycle
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CMBM
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Nucleus Structure & Cell Cycle
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  1. Where is protein synthesized?
    In the cytoplasm, then transported back into the nuclear compartment
  2. What is the composition of nucleus?
    80% protein, 15% DNA, 5% RNA and 3% lipid
  3. What types of proteins are found in the nucleus?
    Enzymes, DNA and RNA polymerases, RNA processing enzymes, histone and non-histone proteins, and other gene regulatory proteins
  4. What is chromatin composed of?
    Protein plus polynucleotide chains with different levels of compaction  (heterochromatin, euchromatin, and at its most compact state csomes)
  5. Nuclear envelope
    Composed of a double trilaminar unit membrane with intramembrane space; the outer membrane of the envelope is continuous with the ER; ribosomes are frequently located on the outer envelope; it is only permeable to small nonpolar molecules
  6. What is the nuclear lamina, what is it composed of, and what are its critical roles?
    Also known as the nuclear matrix; This is a thin, finely fibrillar layer which lies below the inner membrane, providing reinforcement to the nuclear envelope; it is composed of lamins A, B, and C arranged as a meshwork of fine filaments termed intermediate filaments; these filaments serve as attachment sites to the inner nuclear membrane and are critical for structural support; the peripheral chromatin are attached to the nuclear lamina; contributes to the regulation of DNA repair, replication, and transcription
  7. How do Lamins create intermediate filaments?
    First two Lamins twist together, then two sets of twisted Lamins twist around each other (much like a rope); called dimerization
  8. What are laminopathies?
    Rare genetic disorder that result from lamin A/C mutations; can also result from mutated proteins which bind to lamins (emerin)
  9. Atypical Werner syndrome
    Results from a mutation in lamins A/C not from a mutation in the WRN gene; progeria, short stature, cataracts, osteoporosis, vascular disease, and sclerodermatous skin (hardening and tightening of skin); freactures and abnormal bone depositions in the ribs and long bones of the arm associated with progeria
  10. Cardiomyopathy
    Laminopathy resulting in muscle wasting in the heart; leads to heart attack
  11. Congenital Muscular dystrophy
    Laminopathy resulting in muscle wasting during first year of life
  12. Emery Dreifuss muscular dystrophy
    Laminopathy resulting from disrupted interaction between lamin A and the nuclear envelope protein emerin
  13. Werner syndrome
    Mutation in WRN gene; progeria; commonly has beaked nose, baldness, and cataracts
  14. What causes the number of nuclear pores to increase?
    The number of nuclear pores in a cell can vary, but are increased in a proliferating cell
  15. Nuclear pore structure
    You have a nuclear pore complex comprised of ~30 proteins attached to lamina with octagonal symmetry organized around a large central channel; the inner and outer nuclear membrane are continuous with each other around the circumference of the nuclear pore; has an ATP/GTP dependent gate which can either open wider or close shut
  16. What exits through the nuclear pore?
    mRNA and ribosomal subunits synthesized in the nucleus
  17. How do proteins enter the nuclear pore?
    Proteins have a nuclear localization signal (NLS) which attaches to a nuclear transport receptor, also called a cytoplasmic receptor; the nuclear transport receptor attaches to the fibril on the importin, and walks down the fibrils 2 AAs at a time
  18. Nucleolar organizer region (NOR)
    Where all the rRNA genes are coming together
  19. Pars granulosa
    Refers to the part of the nucleolus where ribosomal proteins are assembling with rRNA, creating the ribosomal subunits
  20. Pars fibrosa
    Region where the rRNA is being transcribed from the ribosomal genes
  21. How are the ribosomal subunits created?
    • Ribosomal proteins made in the cytoplasm enter the nucleus and congregate in the nucleolar organizer region (NOR) in the nucleolus, rRNA is transcribed in the pars fibrosa, then the ribosomal proteins and rRNA congregate to form the subunits in the pars granulosa; the small land large
    • subunit exit the nucleus where they congregate to create the mature ribosome
  22. What can multiple nucleoli be indicative of?
    Cancer; seen in cells with active growth and division (cell proliferation)
  23. Centromere
    Kinetochores connect to this constricted region of the DNA; microtubules attach to the kinetochores
  24. Kinase
    Used to phosphorylate objects; have a serine, threonine or tyrosine side chain; transfer phosphates from ATP molecules to proteins (including other kinases) each phase of the cell cycle is regulated by a specific cyclin dependent kinase and a specific cyclin
  25. M-cyclin dependent kinase
    • Mitosis is controlled by MPF (mitosis promoting factor or maturation promoting factor) which is a dimer of cdk1 and Cyclin B; the phosphorylation of mitotic Cdk allows it to bind to M-cyclin (Cyclin B; which is regulated by a ubiquitin tag) and trigger the mitosis machinery; at the end of the phase the M-cdk is inactivated and the M-cyclin with its ubiquitin tag is taken to the
    • proteasome to be destroyed
  26. Proteasome
    Not an organelle, rather a complex of proteins that is responsible for protein degradation and the turnover of short-lived proteins in the cell; proteins have to have a ubiquitin tag to be taken to proteasome; cancer cells have high levels of proteasome activity
  27. What are the actions of MPF?
    Chromatin condensation and nuclear envelope breakdown(cdk1 once activated by cyclin B, turns around and phosphorylates histone one and lamins causing the nuclear envelope to break down); fascilitates the fragmentation of the Golgi, mitochondria, and ER to their proper segregation in the daughter cells; sets up the formation of the mitotic spindle
  28. Retinoblastoma
    • This is the regulatory point in G1; an active unphosphorylated Rb protein prevents progression of the cell cycle past this point; once phosphorylated by the cyclin D-Cdk4 complex, the RB protein is inactivated and
    • you can proceed in the cell cycle
  29. Retinoblastoma (disease)
    RB Loss in normal cells results in tumor in the eye and loss of vision
  30. Platelet derived growth factor (PDGF)
    Proliferation of connective tissue cells
  31. Epidermal growth factor (EGF)
    Proliferation of skin cells
  32. Fibroblast growth factor (FGF)
    Proliferation of fibroblasts
  33. Hepatocyte growth factor (HGF)
    Proliferation of liver cells
  34. Erythropoietin
    Proliferation of developing red blood cells
  35. Signal transduction cascade
    A cascade of phosphorylation and dephosphorylation of proteins that amplifies a signal and results in a specific cellular response
  36. What are permanent cells?
    Cells which can never become another cell type or revert back to a stem cell; neurons, lens of the eye, cardiac muscle, and photoreceptors

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