Theme 4 Module 1

• Cell division


  An important cellular process
• Mitosis


  1. Prophase

  2. Prometaphase

  3. Metaphase

  4. Anaphase

  5. Telophase
• Eukaryotic cell cycle


  • Interphase (S phase, G1 phase, G2 phase)
  • M phase (mitosis and cytokinesis)
• Interphase


  Cell prepares for cell division, including DNA replication
• G0 phase


  Cells pause in the cell cycle, can be short or long term
• Stem cells


  Unspecialized cells that can reproduce indefinitely and differentiate into specialized cells
• Satellite stem cells


  Quiescent stem cells in muscle tissue that can become activated to enable muscle regeneration
• Chromosomes


  Duplicated into sister chromatids during DNA replication in interphase
• Centromere


  Fully replicated but highly compacted during interphase
• Prophase


  Chromosomes condense, centrosomes form mitotic spindle
• Prometaphase


  Nuclear envelope fragments, microtubules attach to kinetochores
• Metaphase


  Chromosomes align at metaphase plate
• Kinetochore


  • Protein structures that associate with each one of the two sister chromatids on either side of the centromere
  • Some of the microtubules that radiate from the centrosome attach directly to the kinetochore regions
  • These kinetochore microtubules are essential to help pull the chromosomes to the poles of the cell during mitosis
• Polar microtubules


  • Other microtubules that also radiate from the centrosome as part of the mitotic spindle
  • These microtubules will interact with each other and help push the poles of the cell away from each other during mitosis
• Metaphase


  1. Alignment of chromosomes at the center of the cell in a region identified as the metaphase plate

  2. Kinetochore microtubules are attached at the kinetochores of each sister chromatid and facilitate this alignment at the metaphase plate
• Anaphase


  1. Kinetochore microtubules begin to shorten and the sister chromatids separate into individual chromosomes that are pulled towards the opposite spindle poles of the cell

  2. Polar microtubules push against each other and help elongate the cell
• Telophase


  1. Nuclear envelope reforms around the chromosomes at the opposite poles of the dividing cell

  2. Chromosomes begin to decondense and spindle microtubules are depolymerized (or are broken down)

  3. Division of one nucleus into two genetically identical nuclei marks the end of mitosis
• Cytokinesis


  1. Formation of a contractile ring made up of motor proteins that contract bundles of actin fibers along the midline of the cell, leading to the formation of a cleavage furrow which separates the cell into two distinct and separate daughter cells

  2. In plant cells, a newly developed cell wall is laid down along a cell plate region in the middle of the dividing cell, and once the forming cell wall fuses with the original cell wall, cytokinesis is then complete
• Mitosis promoting factor


  Allows for the transition from the G2 to M phase of the cell cycle
• Cyclin


  A protein that increases then decreases with each subsequent cell division, playing a regulatory role on cell cycle progression
• Cyclin-dependent kinase (CDK)


  An enzyme that activates or inactivates other proteins by phosphorylating key amino acids, and forms a complex with cyclin to trigger cell cycle events
• Cell cycle regulation


  1. G1/S cyclin-CDK complex is needed for the transition from G1 to S phase and helps prepare the cell for DNA replication

  2. S-cyclin-CDK complex helps initiate DNA synthesis

  3. M cyclin-CDK complex initiates the process of mitosis
• Cell cycle checkpoints


  • Serve as a form of cellular surveillance and can block cyclin-CDK activity if something goes wrong during the cell cycle
  • Include a DNA damage checkpoint at the end of G1 phase, a DNA replication checkpoint at the end of G2 phase, and a spindle assembly checkpoint before anaphase during mitosis
• DNA damage checkpoint


  Protein kinases phosphorylate p53, which can then accumulate in the nucleus and act as a transcription factor to turn on genes that will inhibit the cell cycle, giving the cell an opportunity to repair the damaged DNA
• Spindle assembly checkpoint


  1. Regulatory proteins monitor the degree to which the sister chromatids are attached to microtubules of the mitotic spindle at their kinetochore regions

  2. Unattached kinetochores create a "wait" signal which leads to the recruitment of spindle-assembly checkpoint proteins

  3. These proteins are activated by a lack of tension in the centromere area, and only allow for the progression of metaphase and entry into anaphase when each sister chromatid is attached to a kinetochore microtubule
• Prokaryotes reproduce by binary fission, while eukaryotic cells produce identical daughter cells through mitosis as part of a larger cell cycle
• The DNA of the cell must be replicated so that each daughter cell receives the identical genetic information
• The eukaryotic cell cycle is regulated by cyclin-CDK complexes and various checkpoints that regulate the overall process of cell division
• The cell cycle control mechanisms contribute to the overall chromosome dynamics that are observed in dividing cells
• Genetic factors


  Each type of cell in the body has a unique genetic code that determines its characteristics and functions. When a stem cell divides, the resulting daughter cells can inherit different combinations of genes from the parent cell, which can influence the cell's fate.
• Epigenetic factors


  Epigenetic modifications refer to changes in gene expression that do not involve changes to the underlying DNA sequence. These modifications can be influenced by a variety of factors, including environmental cues, aging, and disease. Epigenetic changes can help to determine which genes are active or inactive in a stem cell, and therefore which cell type it will become.
• Signaling molecules


  Cells in the body communicate with each other through the use of signaling molecules, such as growth factors and cytokines. These molecules can bind to receptors on the surface of a stem cell and trigger a cascade of intracellular signaling events that ultimately influence the cell's fate.
• Microenvironment


  The microenvironment in which a stem cell resides can also play a role in determining its fate. Factors such as the stiffness of the extracellular matrix, the presence of other cells, and the availability of nutrients and oxygen can all influence the behavior of a stem cell.
• Mitosis Promoting Factor (MPF)


  A complex of two proteins, CDK1 and cyclin B, that regulates the transition from the G2 phase to the M phase of the cell cycle
• CDK1


  A cyclin-dependent kinase that is a component of MPF and plays a crucial role in regulating the cell cycle
• Cyclin B


  A regulatory subunit of MPF that is required for its activity during the cell cycle
• G2 phase


  The second growth phase of the cell cycle, during which the cell prepares for mitosis
• M phase


  The mitosis phase of the cell cycle, during which the cell divides into two daughter cells
• Wee1


  A protein kinase that phosphorylates and activates MPF, allowing for the transition from the G2 phase to the M phase of the cell cycle
• Cdc25


  A protein phosphatase that inactivates MPF by removing the phosphate group from CDK1, thereby preventing the transition from the G2 phase to the M phase of the cell cycle