Mitosis ensures accurate distribution of genetic material during cell division. This process involves chromosome condensation, spindle formation, and precise segregation of sister chromatids. Understanding mitosis is crucial for grasping how cells maintain their genetic integrity.

Cytokinesis completes cell division by physically separating daughter cells. While animal cells use a contractile ring, plant cells form a cell plate. Errors in mitosis or cytokinesis can lead to aneuploidy, potentially causing developmental disorders or contributing to cancer progression.

Mitosis and Chromosome Segregation

Stages of mitosis

• Prophase
  • Chromatin condenses into tightly coiled, visible chromosomes (X-shaped structures)
  • Nuclear envelope disintegrates, allowing chromosomes to interact with cytoplasmic components
  • Centrosomes, the main microtubule-organizing centers, move to opposite poles of the cell (animal cells)
  • Mitotic spindle, a bipolar array of microtubules, begins to assemble between the centrosomes
• Metaphase
  • Chromosomes align at the cell's equatorial plane, forming the metaphase plate (imaginary line)
  • Kinetochores, protein complexes on the centromeres of sister chromatids, attach to microtubules emanating from opposite spindle poles
  • Proper attachment of all chromosomes to the spindle triggers the transition to anaphase
• Anaphase
  • Cohesion between sister chromatids is lost as the cohesin complex is cleaved by separase
  • Sister chromatids separate and move towards opposite poles of the cell, becoming individual chromosomes
  • Microtubules shorten (depolymerize), pulling the chromosomes apart and towards the spindle poles
  • Chromosomes move at a rate of ~1-2 μm/min (human cells)
• Telophase
  • Chromosomes reach the spindle poles and begin to decondense, becoming less tightly coiled
  • Nuclear envelope re-forms around each set of chromosomes, creating two distinct nuclei
  • Mitotic spindle disassembles as microtubules depolymerize
  • Cytokinesis, the division of the cytoplasm, begins during telophase (animal cells)

Role of mitotic spindle

• The mitotic spindle ensures equal distribution of genetic material (chromosomes) to daughter cells
• Microtubules, polymers of α- and β-tubulin dimers, are the main components of the spindle
  • Microtubules have a fast-growing plus end and a slower-growing minus end
• Kinetochore microtubules attach to kinetochores on centromeres of sister chromatids
  • Kinetochore microtubules connect chromosomes to spindle poles
  • Proper attachment is essential for accurate chromosome segregation (amphitelic attachment)
• Polar microtubules interdigitate at the cell's equator, providing stability to the spindle structure
  • Polar microtubules from opposite poles overlap and are cross-linked by motor proteins (kinesins)
• Motor proteins, such as dynein and kinesin, generate forces for chromosome movement
  • Dynein moves towards the minus end of microtubules (poleward movement)
  • Kinesin moves towards the plus end of microtubules (anti-poleward movement)
• Microtubule dynamics (polymerization and depolymerization) contribute to chromosome segregation
  • Polymerization pushes chromosomes away from the poles
  • Depolymerization pulls chromosomes towards the poles (Pac-Man mechanism)

Cytokinesis and Mitotic Errors

Cytokinesis in animals vs plants

• Animal cells:
  1. Cleavage furrow forms at the cell's equator, perpendicular to the spindle axis
  2. Contractile ring, composed of actin and myosin filaments, assembles beneath the plasma membrane
  3. Contraction of the ring constricts the cell, forming a cleavage furrow
  4. Furrow ingresses until the cell is pinched into two daughter cells
  5. Midbody, a remnant of the spindle, connects the daughter cells until abscission occurs
• Plant cells:
  1. Phragmoplast, a microtubule-based structure, forms between the two nuclei
  2. Vesicles containing cell wall material (cellulose, hemicellulose, pectin) align along the phragmoplast
  3. Vesicles fuse, forming the cell plate, a new cell wall that will separate the daughter cells
  4. Cell plate expands centrifugally until it fuses with the parent cell wall
  5. Golgi apparatus and endoplasmic reticulum contribute vesicles to the growing cell plate

Consequences of mitotic errors

• Aneuploidy (abnormal chromosome number) can result from mitotic errors
  • Nondisjunction: failure of sister chromatids to separate during anaphase, leading to gain or loss of chromosomes
  • Anaphase lag: a chromosome lags behind during anaphase movement, often due to improper kinetochore attachment
• Aneuploidy is associated with developmental disorders and cancer
  • Down syndrome (trisomy 21): extra copy of chromosome 21, causing intellectual disability and characteristic facial features
  • Turner syndrome (monosomy X): absence of one X chromosome in females, leading to short stature and infertility
  • Many solid tumors exhibit aneuploidy, which can contribute to tumor progression and drug resistance
• Mitotic spindle assembly checkpoint (SAC) monitors kinetochore-microtubule attachments
  • SAC prevents anaphase onset until all chromosomes are properly attached to the spindle (bioriented)
  • Unattached kinetochores generate a "wait anaphase" signal (Mad2, BubR1) that inhibits the anaphase-promoting complex (APC/C)
• Centrosome amplification (>2 centrosomes) can lead to multipolar spindles and chromosome missegregation
  • Extra centrosomes are common in cancer cells and may contribute to genomic instability
  • Clustering of extra centrosomes into two poles can allow cancer cells to undergo bipolar division and survive