Lecture 19

• Cell cycle phases


  • G0
  • G1
  • S
  • G2
  • M
• G0 phase


  1. Inactive cell cycle after mitosis

  2. Usually reversible if growth factors present
• Interphase


  1. G1 phase: cells grow and more organelles produced

  2. S phase: DNA replicated

  3. G2 phase: cell grows and prepares for mitosis
• M phase (mitosis & cytokinesis)

  1. Replicated chromosomes are organized then separated into two daughter cells

  2. Prophase

  3. Prometaphase

  4. Metaphase

  5. Anaphase

  6. Telophase
• Post-mitotic cells


  • Cannot reenter cell cycle when exposed to growth factors
  • Cannot regenerate
• Post-mitotic cells


  • Neurons
  • Eye cells
  • Ear cells
• Interpreting cell cycle phase graphs

  • Dye that becomes fluorescent when bound to DNA
  • X-axis: fluorescence (amount of DNA in cell)
  • Y-axis: number of cells
• Mitogens


  • Growth factors that activate growth factor receptors and induce cells to leave G0 and enter cell cycle
  • Promote active mitosis
• G1 checkpoint


  1. Cell only replicates DNA if growth factors are present and DNA is not damaged

  2. Enter cell cycle and proceed to S phase

  3. Is environment favorable
• G2 checkpoint


  1. Cells only enter mitosis if DNA has been completely replicated and DNA is not damaged

  2. Is all DNA replicated?

  3. G2/M transition

  4. Enter mitosis
• M checkpoint


  1. Replicated chromosomes are segregated in anaphase only if all chromosomes are attached to mitotic spindle

  2. Are all chromosomes attached to the spindle?

  3. Metaphase to anaphase transition

  4. Trigger anaphase and proceed to cytokinesis
• Cyclin-dependent kinase (Cdk)


  Non receptor serine/threonine kinase that activates cell cycle proteins
• Function of cyclin in cell cycle

  • Cyclins activate Cdks and help Cdks find target proteins to phosphorylate
  • Cdks are constantly expressed but only active when cyclin present
  • Cyclins are expressed at specific times during cell cycle and activate specific Cdks
• Regulation of M-Cdk


  1. M-cyclin expression starts at beginning of G2 phase but m-cdk not activated till the end of G2 phase

  2. Wee1 kinase phosphorylates active site of m-cdk which inhibits kinase activity (inactive m-cdk)

  3. Cdc25 phosphatase removes inhibitory phosphate to activate m-cdk
• Cells need high amounts of active m-cdk to surpass G2 checkpoint
• Cdk inhibitors (CKIs)


  • Allow cells to pause cell cycle for regulation or adapt to change (DNA damage)
  • Prevent cell from entering the next phase
  • For ex] CKI keeps S-cdk-cyclin complex inactive during late G1 phase
• Regulation of cyclins


  1. Some cyclins are degraded by the proteosome

  2. Cdk activity needs to be regulated so checkpoint is passed at appropriate times
• Function of anaphase promoting complex (APC)


  APC is an E3 ub ligase that polyubiquitylates m-cyclins which inactivate m-cdk at end of mitosis