Nucleus and DNA organization

• Why did the nuclear envelope evolve?

  • protect internal components
  • Prevent interference
• Parts of the nucleus

  • Chromosome
  • Nucleoli
  • Nucleoplasm
  • Nuclear matrix
• Parts of nuclear membrane

  • nuclear envelope
  • nuclear lamina
  • nuclear pore complexes
• Nuclear envelope serves as a barrier to regulate ions, solutes, and macromolecules entering and exiting the nucleus; also establishes a concentration gradient
• Inner nuclear membrane contains 60 integral proteins that binds the nuclear lamina; where lamina is anchored
• Outer nuclear membrane continuous with the ER and is generally studded with ribosomes as well; has a similarity with ER in terms of the membrane
• Nuclear lamina gives mechanical support to the nuclear envelope; serves as site of attachment for chromatin fbers
• Lamina is composed of polypeptides called lamins (10nm intermediate fbers; since it is an intermediate flament it can then form a higher order structure)
• Prenylation

  • post-translational modification
  • adds a non-polar farnesyl group so that it can be anchored to the nuclear envelope
• LINC

  • Linker of Nucleoskeleton and Cytoskeleton complex
  • Can interact both to the inside and outside of the nucleus
• NPC - nuclear pore complexes
• NPC

  • Composed of 30 different nucleoporins/nucleoproteins (NUPs)
  • forms perforation in nuclear envelope to allow the transport of essential macromolecules
• T or F: number of NPCs vary with the activity of nucleus

  True
• T or F: activity increases, the number of NPCs increase as well

  True
• Inactive cells

  • hundred/nucleus

  Active body cells

  • thousands/cells

  Highly active cells

  • 50 million/nucleus
• NPCs can transport macromolecules in a bidirectional manner
• Transport within NPCs

  A) passive diffusion

  B) selective transport

  
• Molecules involved for transport into the nucleus

  • Nuclear localization signal (NLS)
  • Nuclear transport receptors (karyopherins)
  • RAN-GTP or RAN-GDP
  • Ran GAP
  • Ran-GEF
• Part of the nuclear protein that, when detected, allows the entry to the nucleus

  NLS
• T or F: alternation of the NLS prevents the entry of that molecule

  T
• Karyopherins (into the nucleus)

  • Importin
  • NTF
• Karyopherins (out of the nucleus)

  • Exportin
  • NTF2
• molecules involved for transport out of the nucleus

  • Nuclear Export Signal (NES)
  • Karyopherins
  • RAN-GTP or RAN-GDP
  • RAN GAP
  • RAN-GEF
• How does the nuclear membrane lose its integrity?

  phosphorylation of lamins
• • dephosphorylation restores the integrity of lamins and nuclear envelope
• Nuclear matrix

  • network of thin protein-containing fbrils criss-crossing through the nuclear space
  • maintains the shape of the nucleus and served to anchor the machinery for the various activity of the nucleus
• Nucleosome is the first and most basic level of chromosome packing where DNA is wrapped around the histone
• Histone are the beads on a string
• T or F: the structure of nucleosome consists of 8 histone proteins

  True
• Structure of nucleosome

  • 2 H2A-H2B dimer
  • 2 H3-H4 dimer
  • DSDNA
• T or F: There is a high content of lysine and arginine in histones

  True
• 5 Classes of histones

  • H1
  • H2A
  • H2B
  • H3
  • H4
• T or F: chromatin is composed of DNA and proteins

  True
• Types of heterochromatin

  • Constitutive heterochromatin - permanently silenced
  • Facultative heterochromatin - inactive at specific phases
• Proteins involved in pre-mRNA processing are localized to discrete sites called speckles