Mitosis

• What is karyotype?


  Individual's number & structure of the chromosomes (e.g, 46,XY)

  (display of chromosomes of a somatic cell during metaphase)

  
• Examples of abnormal chromosome numbers (aneuploidy):


  • Turner syndrome (women with 1 X chromosome) XO Monosomy X (45,XO)
  • Klinefelter syndrome (XXY instead of XX/XY- extra copy of X) 47,XXY
  • Down syndrome- trisomy of chromosome 21 47,XX + 21
• What is chromatin?


  DNA entangled with histone proteins
• What are chromatids?


  Newly copied chromosome still joined by centromere (chromosome in prophase to metaphase)
• What is a nucleosome?


  Combined tight loop of DNA & 8 histone proteins

  Nucleosomes stack on top of eachother to form chromatin
• Prophase:


  Chromosome condensation

  Duplicated DNA strands (packaged into elongated chromosomes) condense into more compact chromosomes. Nuclear envelope breaks down.
• Prometaphase:


  Replicated chromosomes (each consisting of a pair of sister chromatids) become attached to microtubules of mitotic spindle.
• Metaphase:


  Chromosomes aligned at equator of mitotic spindle, poised for separation
• Anaphase:


  Separation of sister chromatids (chromosomes move to opposite poles of spindle)
• Telophase:


  Chromosomes de-condense & nucleus reforms
• Cytokinesis:


  Cytoplasm divides
• G2 phase:


  • Transition from S to M phase
  • Check for errors in DNA replication
  • May not be clear in some cells e.g, when cells dividing rapidly (e.g, some of embryonic & cancer cells)
• What does DNA helicase do in DNA replication?


  Unwinds double stranded DNA
• What does DNA polymerase do in DNA replication?


  Elongates new strand by incorporating free nucleotides

  Synthesises DNA from 5 prime to 3 prime direction
• What does DNA ligase do in DNA replication?


  Joins Okazaki fragments (fragmental DNA)
• G1 phase:


  • Cells monitor internal condition & external signals to decide for cell differentiation &/or timings of next cell division
  • DNA packed in form of chromatin
  • Cells may enter a quiescent state (G0) where they can remain as non-dividing cells for days to years
• Interphase:


  G1, S & G2
• S-phase:


  • DNA duplicated
  • DNA double strands unwind & each strand replicated
  • New strands coiled around histones & from chromatin again (ready for G2 phase)
  • Centrosomes duplicated
• Purine:


  A & G
• Pyrimidine:


  C & T
• What is mitosis useful for?


  • Increases number of cells (development & growth e.g, during embryogenesis)
  • Tissue maintenance & repair (in adult life, some cells continuously divide e.g, in gut, skin & hair growth)
• What are stem cells?


  • Undifferentiated cells that are yet to specialise
  • Some cell types in adult tissues show a regular turn-over by stem cells
  • Cells regularly replaced e.g, in skin, gut & hair
  • Stem cell divide & proliferate quickly
• What is an aster?


  Star-shaped array of microtubules emanating from a centrosome or from a pole of a mitotic spindle.
• Which types of cells are in G0?


  • Most adult neurons & skeletal muscle cells (can be replaced by stem cells)
  • Most liver cells (can regenerate by cell division if liver damaged)
• Why do cancer cells proliferate in a dysregulated manner?

  • Genetic mutations that normally control cell cycle checkpoints
  • Apoptosis
  • Mutations in P53 (tumour suppressor gene) that normally induces cell death when DNA damaged
• Types of anti-cancer drugs:

  • Block DNA synthesis (S phase)
  • Block mitotic spindle formation/contraction (M phase)
  • Block cyclin-dependent kinases (CDKs) that promote check points (cells don't go further in cell cycle)
  • Block specific signal transduction pathways (specific to cancer cells)
• What are CHKs?


  Checkpoint kinases involved in cell cycle control
• How many reading frames are there for a DNA double helix?

  6 (3 possible ways)

  Find out which frame valid due to how many stop codons are in sequence (should be less/none)

  All proteins start with codon ATG (MET)
• Where are untranslated regions?

  Ends of 5' & 3'
• How do we write down DNA sequence?

  5' to 3' (omit complementary strand)