Revise Chromosome behaviour in mitosis for Cambridge 9700 (5.2)

The life of a eukaryotic cell is described by the cell cycle, a regulated sequence of growth and division. It consists of two main phases: Interphase, a long period of growth and DNA replication, and the M (Mitotic) Phase, where the cell divides its nucleus (mitosis) and cytoplasm (cytokinesis).

Interphase is the longest phase of the cell cycle, during which the cell is highly metabolically active. It is subdivided into three stages:

• G₁ (First Gap) Phase: The cell grows in size and synthesises proteins and RNA. Organelles are duplicated. A critical checkpoint at the end of G₁ ensures the cell is ready to commit to division.
• S (Synthesis) Phase: The cell's DNA is replicated. Each chromosome, initially a single DNA molecule, is duplicated to form two identical sister chromatids joined at a region called the centromere. The amount of DNA in the cell doubles.
• G₂ (Second Gap) Phase: The cell continues to grow and produce proteins, particularly tubulin, which is required for the formation of the mitotic spindle. The replicated DNA is checked for errors, and repairs are made. Another checkpoint ensures the cell is ready to enter mitosis.

Mitosis is a continuous process divided into four distinct stages for ease of description.

Prophase

This is the first and often longest stage of mitosis. Key events include:

• Chromatin Condensation: The long, tangled chromatin fibres coil and supercoil, becoming shorter, thicker, and visible under a light microscope as distinct chromosomes. Each chromosome consists of two sister chromatids.
• Nuclear Envelope Breakdown: The nuclear envelope and nucleolus disintegrate.
• Spindle Formation: In animal cells, the two centrosomes (which replicated during interphase) move to opposite poles of the cell. Microtubules extend from them to form the mitotic spindle. Plant cells lack centrioles but still form a spindle from microtubule-organising centres (MTOCs).

Metaphase

During this short phase, the chromosomes are maximally condensed.

• Chromosome Alignment: The chromosomes line up along the cell's equator, forming the metaphase plate.
• Spindle Fibre Attachment: Spindle fibres (kinetochore microtubules) from opposite poles attach to the kinetochore (a protein structure) at the centromere of each chromosome. The tension from these opposing fibres holds the chromosomes in place.

Anaphase

This is the shortest and most dynamic stage.

• Sister Chromatid Separation: The proteins holding the sister chromatids together are cleaved. The centromeres divide, and the sister chromatids separate.
• Chromosome Migration: Each chromatid is now considered an individual chromosome. The kinetochore microtubules shorten, pulling the newly separated chromosomes towards opposite poles of the cell, centromere first.

Telophase

Telophase is essentially the reverse of prophase.

• Chromosome Decondensation: The chromosomes arrive at the poles and begin to uncoil and decondense back into their diffuse chromatin state.
• Nuclear Envelope Reformation: A new nuclear envelope forms around each of the two sets of chromosomes, creating two new nuclei.
• Spindle Disassembly: The mitotic spindle breaks down.

Cytokinesis usually begins during late anaphase or telophase and completes the cell division process.

• In Animal Cells: A cleavage furrow forms at the cell surface. This is caused by a contractile ring of actin and myosin filaments, which tightens and pinches the parent cell into two daughter cells.
• In Plant Cells: Due to the rigid cell wall, a cleavage furrow cannot form. Instead, vesicles from the Golgi apparatus gather at the metaphase plate and fuse to form a cell plate. This plate grows outwards, eventually fusing with the existing cell wall and dividing the cell in two.

Mitosis is fundamental to life for several critical reasons:

• Growth: It increases the number of cells in a multicellular organism, leading to growth from a zygote to an adult.
• Repair and Replacement: It replaces damaged or old cells (e.g., skin cells, red blood cells) and repairs tissues after injury, maintaining tissue integrity.
• Asexual Reproduction: In many unicellular (e.g., Amoeba) and some multicellular organisms (e.g., vegetative propagation in plants), mitosis is the basis of asexual reproduction.
• Genetic Stability: Crucially, mitosis produces two genetically identical daughter cells from a single parent cell. This means the diploid (2n) chromosome number and the exact genetic make-up are maintained across generations of cells, ensuring consistent function and characteristics within an organism.

The cell cycle is not a simple, automatic process; it is tightly regulated by a molecular control system involving checkpoints and regulatory proteins. The key players are cyclins and cyclin-dependent kinases (CDKs).

• CDKs are enzymes that are always present in the cell but are only active when bound to a cyclin protein.
• Cyclins are proteins whose concentrations fluctuate cyclically throughout the cell cycle.
• When a specific cyclin binds to its corresponding CDK, the resulting complex phosphorylates target proteins, triggering progression to the next phase of the cycle. For example, the maturation-promoting factor (MPF) complex (a cyclin-CDK complex) triggers the G₂ to M phase transition. These control mechanisms ensure that each stage is completed correctly before the next begins.

Cancer is fundamentally a disease of the cell cycle. It arises from a loss of the normal control mechanisms that regulate cell division. Mutations in two types of genes are often responsible:

• Proto-oncogenes: These genes normally code for proteins that stimulate cell division. When mutated, they can become oncogenes, leading to over-stimulation and uncontrolled proliferation.
• Tumour Suppressor Genes: These genes normally code for proteins that inhibit cell division or trigger apoptosis (programmed cell death) if DNA damage is detected (e.g., the p53 gene). If these genes are mutated and inactivated, the 'brakes' on cell division are lost. Multiple mutations are usually required for a cell to become cancerous, leading to the formation of a mass of abnormal cells called a tumour.