LEC 16: Mitosis, Chromosome Segregation, and Cell Cycle Control

The Cell Cycle and Mitosis

Overview of Mitosis

Mitosis is the process by which eukaryotic cells divide their genetic material to produce two genetically identical daughter cells. This process ensures accurate segregation of chromosomes and is tightly regulated by the cell cycle.

• Chromosome Segregation: Sister chromatids are held together by protein complexes called cohesins until the onset of anaphase.

• Spindle Apparatus: Microtubules attach to chromosomes at the kinetochore, generating tension and facilitating movement.

• Metaphase Plate: Chromosomes align at the cell's equatorial region, forming the metaphase plate.

Cohesin and Chromatid Cohesion

Cohesin is a protein complex that forms a ring structure, embracing the two sister chromatids and holding them together until anaphase. The regulation of cohesin is crucial for proper chromosome segregation.

• Protector Protein (Securin): Prevents premature destruction of cohesin.

• Separase: An enzyme that cleaves cohesin, allowing sister chromatids to separate.

• Anaphase-Promoting Complex (APC): Triggers the degradation of securin, activating separase.

Sequence of Events:

1. Before anaphase, securin inhibits separase, keeping cohesin intact.

2. At anaphase onset, APC degrades securin.

3. Separase becomes active, cleaving cohesin and enabling chromatid separation.

Metaphase and Anaphase

During metaphase, chromosomes are aligned at the metaphase plate, and cohesins remain intact. Once all chromosomes are properly attached to spindle microtubules, the cell transitions to anaphase.

• Anaphase: The shortest stage of mitosis, initiated by the cleavage of cohesin proteins.

• Mechanisms of Chromatid Segregation:

  • Anaphase A: Shortening of kinetochore microtubules pulls chromatids toward spindle poles.

  • Anaphase B: Spindle poles (centrosomes) move apart, further separating chromatids.

Tension and Movement: Tension is generated by microtubules pulling in opposite directions. Once cohesin is cleaved, tension is released, and chromatids move rapidly apart.

Telophase and Cytokinesis

Telophase marks the reformation of the nuclear envelope and the decondensation of chromosomes. Cytokinesis is the division of the cytoplasm, resulting in two distinct daughter cells.

• Telophase:

  • Two daughter nuclei form.

  • Nucleoli reappear.

  • Chromosomes de-condense.

  • Spindle microtubules depolymerize.

• Cytokinesis in Animal Cells: An actin-based contractile ring forms at the membrane, and myosin motors use ATP to constrict the ring, forming a cleavage furrow.

• Cytokinesis in Plant Cells: A cell plate forms from vesicles, eventually developing into a new cell wall that separates the daughter cells.

Cell Cycle Control and Checkpoints

Regulation of Cell Division

Eukaryotic cells regulate division through a series of checkpoints that ensure each phase is completed accurately before proceeding. This regulation is essential for maintaining genomic integrity and preventing uncontrolled cell division.

• Unidirectional Progression: The cell cycle moves forward only; checkpoints prevent progression if conditions are not met.

• Major Checkpoints:

  • G1/S Checkpoint: Assesses whether the cell should divide, often in response to external signals called growth factors (e.g., Platelet-derived growth factor, PDGF).

  • G2/M Checkpoint: Ensures DNA replication is complete and undamaged before mitosis.

  • M Checkpoint (Spindle Checkpoint): Ensures all chromosomes are properly attached to the spindle before anaphase begins.

• G0 Phase: If a cell does not receive the appropriate growth signal at G1, it may enter a non-dividing state called G0.

Example: In the absence of growth factors, such as PDGF, cells may remain in G0 and not proceed to divide, which is a key mechanism in tissue maintenance and repair.

Additional info: The coordination of cell cycle checkpoints is crucial for preventing mutations and cancerous growth. Disruption of checkpoint control is a hallmark of many cancers.