Cell Division Cycle

Cell-Division Cycle Study Notes

Cell Cycle

  • Definition:
    • Universal process of cellular reproduction
    • Series of ordered events leading to:
    • Duplication of cellular contents
    • Division into two new "daughter" cells
  • Characteristics:
    • Many features common to all cells.
    • Specific differences exist between:
    • Different organisms
    • Cell types within the same organism
    • Life stages

Fundamental Processes

G1 Phase
  • Definition: G1 = "Growth 1"
    • Immediately follows previous cell division.
  • Activities:
    • Synthesis of proteins and macromolecules.
    • Formation and growth of organelles.
    • Formation and growth of plasma membrane.
  • Function:
    • Monitor and evaluate progress towards "maturity".
G0 Phase
  • Definition: G0 = "0 growth"
    • Optional resting phase in the cell cycle.
S Phase
  • Definition: S phase = "synthesis"
    • New DNA is synthesized during this phase.
G2 Phase
  • Definition: G2 = "growth 2"
    • Additional synthesis of proteins and macromolecules occurs.
M Phase
  • Definition: M phase = mitosis
    • Key events:
    • Segregation of replicated DNA
    • Cytoplasmic division occurs initially during early to mid-mitosis
    • Cytokinesis happens at the end of mitosis, marking the beginning of two new G1 phases.

Checkpoints

  • Function:
    • Processes may be stopped at almost any time if there is:
    • Improper completion of some process
    • Issues with the cell (permanent stop)
    • Environmental signals (temporary or permanent stop)
  • Negative signaling:
    • A 1% negative signal can outweigh 99% of positive signals.
    • More accurately represents a "lack" of positive signaling.

Cell Cycle Control System

  • Structure:
    • An ordered series of biochemical switches.
  • Kernel:
    • Based on "cyclically activated" cell-cycle kinases.
  • Cell-cycle kinases:
    • These phosphorylate proteins involved in various aspects of cell cycle control.
  • Types of kinases:
    • Many types with each phosphorylating different proteins.
    • Phosphorylated target proteins can initiate, inhibit, or modify cell cycle processes.
Cyclin and Cdk Interaction
  • Cyclins:
    • Many types of cyclins exist, each specific to a different family of Cdk.
    • Cyclin-dependent kinases (Cdk’s) require binding with cyclin for activity.
  • Cyclin levels:
    • Cyclins undergo cyclical synthesis and degradation, while Cdk levels remain constant.
Activation and Modification of Cdk's
  1. Cdk Activating Kinase (CAK):
    • Phosphorylates ATP-bound Cdk, activating it.
  2. Cdk Inhibiting Proteins (CKI's):
    • Bind to Cdk, altering its structure and inactivating it.
  3. Wee 1 Kinase:
    • Adds an inactivating phosphate to Cdk, preventing it from transferring an original phosphate.
  4. Cdc 25 Phosphatase:
    • Removes the inactivating phosphate added by Wee 1, thereby reactivating Cdk.

Activation of Cdk

  • Requirements for activation:
    • Appropriate cyclin levels to form cyclin-Cdk complex.
    • CAK must activate the phosphate on cyclin-Cdk without additional phosphorylation from Wee 1 or CKI binding.

Control of Cyclin Levels

  • Synthesis:
    • Controlled through gene expression and translation of cyclin mRNA.
  • Degradation:
    • Ubiquitins added to cyclins by ubiquitin ligases target cyclins for degradation.

Control of DNA Replication

  • Rules for replication:
    • Each nucleotide must be duplicated once and only once.
    • Cells in G2 cannot replicate DNA even when presented with S-phase growth factors.
  • Replication origins (RO's):
    • Spaced throughout the genome and recognized by the origin recognition complex (ORC).
  • Replication initiation:
    • ORC locates and binds to RO's, attracting essential proteins (Cdc6, Mcm) to form the pre-replicative complex.

The Mechanics of Cell Division

Mitosis and Cytokinesis
  • Mitosis:
    • Segregation of duplicated chromosomes.
  • Cytokinesis:
    • Splitting of the cytoplasm into two halves, facilitated by the contractile ring (animals) or phragmoplast (plants).
Chromosome Structure
  • At the end of S-Phase:
    • Chromosomes are replicated with identical sister chromatids held together by cohesin complexes and are compacted by condensins.
Cytoskeletal Machineries
  • Mitotic spindle:
    • Composed of microtubules and associated proteins, vital for chromosome segregation.
  • Contractile ring in animals:
    • Composed of actin and myosin, forming the mechanism for cell division.
  • Phragmoplast in plants:
    • Constructs a new cell wall between dividing nuclei utilizing vesicles carrying cell wall components.

Asymmetrical Division

  • Asymmetry in division:
    • Some cells reposition their spindle to force unequal division of daughter cells, essential for differentiation and development.
  • Example:
    • Seen in early developmental stages or in plant cells to segregate fate determinants.
Physiology of Cell Division
  • Mechanism of the contractile ring:
    • Constriction mechanism similar to muscle contraction but involves highly dynamic actin filaments.
  • Organelle distribution:
    • Organelles like mitochondria and chloroplasts are sorted to ensure adequate distribution, while the ER and Golgi undergo fragmentation during M-phase and participate in the organization of organelles during telophase.

The Phragmoplast in Plants

  • Formation of the phragmoplast:
    • Takes place after telophase with mitotic spindle. Vesicles carrying components accumulate and ultimately fuse to form a new cell wall between daughter cells.
  • Cytokinesis in plants:
    • Complexity due to rigid cell walls requiring the precise formation of new walls using the phragmoplast and newly synthesized vesicles.