Cell Cycle and Mitosis

Overview of Cell Cycle

• The cell cycle consists of four main phases:
  • G1 phase - the cell grows and prepares for DNA synthesis.
  • S phase - DNA is replicated, forming sister chromatids.
  • G2 phase - the cell prepares for mitosis.
  • M phase (Mitosis) - the cell divides its copied DNA and cytoplasm to form two new cells.

Cleavage Divisions

• Prokaryotes do not undergo traditional cell cycles and division (binary fission) lacks G1 and G2 phases.
• Eukaryotic cleavage divisions ensure proper reproduction and inheritance of genetic materials.

Cell Cycle Control System

• Functionality:
  • Coordinates various steps of cellular reproduction among eukaryotic cells.
  • Monitors the timing of events and ensures each phase is completed orderly.
  • Adapts to different cell types and signals originating from outside the cell.
• Checkpoints:
  • Cellular checkpoints help in monitoring the cycle, ensuring that damage or errors prevent progression until issues are resolved.

Cyclin-Dependent Protein Kinases (Cdks)

• Role:
  • Cyclins activate Cdk proteins, crucial for cell cycle progression.
• Types of Cyclins:
  • G1-Cdk (regulates the decision to move into S phase).
  • G1/S-Cdk (triggers the transition from G1 to S phase).
  • S-Cdk (initiates DNA replication).
  • M-Cdk (regulates entry into mitosis).

Mechanism of Cyclin Activation

• Cdk Activation:
  • Cyclins bind to Cdks, which makes the active site of Cdk available for substrate binding.
  • Cdk-activating kinase (CAK) phosphorylates specific sites for complete activation.

Regulation of Cdk Activity

• Phosphorylation Levels:
  • Activity fluctuations are directed by the levels of cyclins and regulatory protein inhibitors (CKIs).
  • Dephosphorylation by Cdc25 can reactivate Cdks.

Cell Cycle Checkpoints

• Definition:
  • Regulatory points in the cell cycle that ensure proper transitions occur.
• Examples of Checkpoints:
  • G1 checkpoint (checks for DNA damage, nutrient sufficiency).
  • G2 checkpoint (checks for DNA replication completeness).
  • M checkpoint (checks spindle attachment during mitosis).

p53 Protein and DNA Damage Response

• Role of p53:
  • Activates transcription of CKIs like p21 upon DNA damage detection, inhibiting G1/S-Cdk and S-Cdk.
• Mechanism of Action:
  • Phosphorylation of p53 leads to activation and transcriptional upregulation of inhibitors, effectively blocking the cycle.

Mitosis Process

• Preceded by proper DNA replication during the S phase facilitated by S-Cdk.
• M-Cdk Role:
  • Triggers the condensation of chromosomes, breakdown of the nuclear envelope, and assembly of the mitotic spindle.

Sister Chromatids and Cohesion

• Cohesins:
  • Protein complexes that hold sister chromatids together until anaphase.
  • Condensins assist in coiling the DNA for easier segregation.

Mitotic Spindle Dynamics

• Type of Microtubules:
  • Kinetochore microtubules connect to chromatids and move them to poles.
  • Interpolar microtubules maintain spindle structure and separate poles during anaphase.
  • Astral microtubules anchor spindle and assist in moving chromatids.

Anaphase Mechanism

• Anaphase A and B:
  • Anaphase A: Chromosomes are pulled towards poles (kinetochore shortening).
  • Anaphase B: Poles are pushed apart via force generated between interpolar microtubules.
• Role of APC:
  • Anaphase-Promoting Complex (APC) activates separase to degrade cohesins and allow sister chromatids to separate.

Exit from Mitosis

• Involves the degradation of M-cyclins via ubiquitin-mediated processes, leading to cell cycle inactivation.
• This regulation allows M-cyclins to accumulate again for future cell cycles.