The Nucleus

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  • The Nucleus
    • What?
      • Double membrane
      • Supported by fibrous protein mesh
      • Aquesous solution containing DNA, RNA and Proteins
    • Why?
      • Separate fragile chromosomes from cytoskeletal cytoplasmic filaments
      • Separate Transcription from Translation
        • RNA processing
        • Regulation of RNA export
        • Regulate export/import of other proteins
    • DNA
      • Phosphodiester bond
        • Nucleotides linked by a covalent bond between 5' phosphate and 3' OH
        • Sugar-Phosphate backbone of DNA
        • Double Helix
      • Store of genetic information
        • Replication
          • 2 strands separate, both forming templates
          • Semi-conservative; each new strand of DNA has one original strand
      • Gene Expression
        • Regulatory sequences say where transcription starts
        • DNA strands separate (Transcription bubble)
        • One strand acts as a template for RNA synthesis
    • Chromosomes
      • Structure
        • Centromeres
          • attaches to mitotic spindle
          • repetitive sequences
          • Heavily Packaged
          • Hold metaphase chromosomes together
        • Telomeres
          • Protective end of chromosome
          • Special replication mechanism
          • Shorten with age
      • Nucleosomes
        • core nucleosomes made up of histone proteins
          • 2 of each 4 proteins make up the histone octomer (H2A,H2B, H3, H4)
          • Hydrogen bonds form between DNA and histone octomer
          • Beads on a string - arrangement of condensed chromatin
      • thread to fibre
        • H1 histone binds to nucleosome
        • interactions between the 4 core histones help
        • 10x packaging factor
      • Looped Domains
        • Structural proteins cause more packaging
      • Further Condensing
        • condensin proteins use ATP to further wind chromatin
        • 10000x packaging factor
    • Nuclear Import
      • Import receptors bind to nuclear localisation signal on cargo
      • Complex then binds to proteins on the cytoplasmic filaments of the nuclear pore complex
      • Sequentially binds to proteins further and further towards the nuclear side of the pore complex
      • GTP causes a change in importin, complex breaks
      • importin/GTP complex returns to cytoplasm
      • GTP hydrolysed to GDP (transported back to the nucleus)
      • importin released to continue cycle again
    • Nuclear Lamina
      • Fibrous meshwork that provides support for the nucleus
        • extends in a loose meshwork
      • Comprised of fibrous proteins called lamins
        • Like other intermediate filaments, lamins associate with each other to form a higher order structure
          • lipid like structures on the lamina bind it to the inner nuclear membrane
      • binds to chromatin through histones H2A and H2B
  • 3x packaging factor
    • Nucleosomes
      • core nucleosomes made up of histone proteins
        • 2 of each 4 proteins make up the histone octomer (H2A,H2B, H3, H4)
        • Hydrogen bonds form between DNA and histone octomer
        • Beads on a string - arrangement of condensed chromatin
  • Nuclear Envelope
    • The Nucleus
      • What?
        • Double membrane
        • Supported by fibrous protein mesh
        • Aquesous solution containing DNA, RNA and Proteins
      • Why?
        • Separate fragile chromosomes from cytoskeletal cytoplasmic filaments
        • Separate Transcription from Translation
          • RNA processing
          • Regulation of RNA export
          • Regulate export/import of other proteins
      • DNA
        • Phosphodiester bond
          • Nucleotides linked by a covalent bond between 5' phosphate and 3' OH
          • Sugar-Phosphate backbone of DNA
          • Double Helix
        • Store of genetic information
          • Replication
            • 2 strands separate, both forming templates
            • Semi-conservative; each new strand of DNA has one original strand
        • Gene Expression
          • Regulatory sequences say where transcription starts
          • DNA strands separate (Transcription bubble)
          • One strand acts as a template for RNA synthesis
      • Chromosomes
        • Structure
          • Centromeres
            • attaches to mitotic spindle
            • repetitive sequences
            • Heavily Packaged
            • Hold metaphase chromosomes together
          • Telomeres
            • Protective end of chromosome
            • Special replication mechanism
            • Shorten with age
        • thread to fibre
          • H1 histone binds to nucleosome
          • interactions between the 4 core histones help
          • 10x packaging factor
        • Looped Domains
          • Structural proteins cause more packaging
        • Further Condensing
          • condensin proteins use ATP to further wind chromatin
          • 10000x packaging factor
      • Nuclear Import
        • Import receptors bind to nuclear localisation signal on cargo
        • Complex then binds to proteins on the cytoplasmic filaments of the nuclear pore complex
        • Sequentially binds to proteins further and further towards the nuclear side of the pore complex
        • GTP causes a change in importin, complex breaks
        • importin/GTP complex returns to cytoplasm
        • GTP hydrolysed to GDP (transported back to the nucleus)
        • importin released to continue cycle again
      • Nuclear Lamina
        • Fibrous meshwork that provides support for the nucleus
          • extends in a loose meshwork
        • Comprised of fibrous proteins called lamins
          • Like other intermediate filaments, lamins associate with each other to form a higher order structure
            • lipid like structures on the lamina bind it to the inner nuclear membrane
        • binds to chromatin through histones H2A and H2B
    • 2 concentric membranes
    • contigous but functionally distinct
    • inner membrane attaches to nuclear lamina and chromatin
    • outer membrane continuous with endoplasmic reticulum
    • Nuclear Pore Complex
      • Regulate flow of molecules in and out of the nucleus
        • RNA molecules and ribosome subunits out
        • Nuclear proteins and ribosome subunit in
      • small molecules diffuse
      • Large molecules are actively transported

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