A Level Biology CIE: The Mitotic Cell Cycle

Chromosome Structure and Components

General Composition - Chromosomes are comprised of a single, exceptionally long DNA molecule that is highly condensed. - In eukaryotic cells, this DNA molecule is associated with proteins. - The combination of DNA and proteins is referred to as chromatin. This is the substance that makes up chromatids and, consequently, chromosomes.
Proteins in Chromosomes - Histones: These are the primary proteins present. They are large, globular, and positively charged. Their specific role is to organise and condense the DNA tightly to ensure it fits within the nucleus. - Enzymes: Other proteins present include enzymes specifically involved in the copying (replication) and repairing of DNA.
Replication and Chromatids - During the S phase of interphase, DNA replicates. - This results in two identical strands of DNA known as chromatids. - These two strands are joined at a narrow region called the centromere. - The pair is referred to as sister chromatids. - Implication for Mitosis: It is vital that sister chromatids are identical (containing the same genes) because during mitosis, one chromatid is distributed to each daughter cell, ensuring they are genetically identical. - Each individual chromatid is composed of one long, condensed DNA molecule containing a series of genes.
Telomeres - The ends of chromatids are "sealed" with protective structures called telomeres.

The Biological Significance of Mitosis

Definition: Mitosis is nuclear division that produces two genetically identical daughter nuclei, which are also genetically identical to the parent nucleus.
Biological Processes Dependent on Mitosis - Growth of Multicellular Organisms: Since the daughter cells are clones (genetically identical with the same chromosome number as the parent), unicellular zygotes can grow into multicellular organisms. Growth occurs across the whole body or in specific regions like meristems (growing points) in plants. - Replacement of Cells & Repair of Tissues: Damaged tissues are repaired through mitosis followed by cell division. Dying cells are continually replaced by identical ones. In humans, this is rapid in the skin and gut lining. - Regeneration: Some animals can regenerate entire body parts; for instance, zebrafish can regenerate fins, and axolotls can regenerate legs and tails. - Asexual Reproduction: This is the production of new individuals from a single parent. - Unicellular organisms (e.g., Amoeba) reproduce via cell division. - Multicellular organisms may produce offspring that "bud off" from the parent. Examples include budding in Hydra and yeast, or runners produced by strawberries.

The Cell Cycle and Interphase

The Cell Cycle Overview - The cell cycle is the regulated sequence of events between one cell division and the next. - It consists of three main phases: interphase, mitosis (nuclear division), and cytokinesis (cell division). - Movement between phases is triggered by chemical signals called cyclins.
Variable Lengths of the Cell Cycle - Cell cycle duration depends on environmental conditions, cell type, and the organism. - Onion root tip cells: Divide roughly once every $20\,\text{hours}$ . - Human intestine epithelial cells: Divide roughly once every $10\,\text{hours}$ .
Stages of Interphase - During interphase, the cell increases in mass/size and performs normal functions (protein synthesis, DNA replication). - $G_1$ Phase (Gap 1): Cells make RNA, enzymes, and proteins required for growth. At some point, a signal is received telling the cell to divide. Protein synthesis is high here; transcription occurs, producing the most mRNA molecules. - $S$ Phase (Synthesis): The DNA in the nucleus replicates. Each chromosome then consists of two identical sister chromatids. This phase is relatively short. - $G_2$ Phase (Gap 2): The gap between the $S$ phase and the next division. The cell continues to grow, synthesised DNA is checked and repaired, and preparations for division are made (e.g., production of tubulin protein for the mitotic spindle). - Formula: $\text{Interphase} = G_1 + S + G_2$
Mitosis (M Phase) and Cytokinesis - M Phase: Nuclear division occurs; cell growth stops. - Cytokinesis: Follows mitosis. The whole cell divides to create two daughter cells. - In animal cells, this involves the constriction of the cytoplasm. - In plant cells, a new cell wall is formed.

The Role and Mechanism of Telomeres

Structure and Composition - Telomeres are made of non-coding DNA consisting of short base sequences repeated many times (multiple repeat sequences). - One strand is rich in guanine (G), and the complementary strand is rich in cytosine (C).
Necessary Function - DNA copying enzymes cannot run to the very end of the DNA molecule; they stop slightly short. - Telomeres act as a "buffer" of non-essential DNA. This ensures that the ends of DNA molecules are included in replication without losing essential gene information. - Without telomeres, vital genes would be lost during division, potentially causing cell death.
Telomerase - Most cells possess the enzyme telomerase, which adds additional bases to the telomeres to "top them up." - Specialised cells that lack telomerase eventually die after a certain number of divisions, a process linked to ageing.

Stem Cells and Potency

Definition: A stem cell can divide via mitosis an unlimited number of times. Each new cell can remain a stem cell or become a specialised cell through differentiation.
Levels of Potency - Totipotency: These cells can differentiate into any cell type found in an embryo as well as extra-embryonic cells (e.g., placenta). Examples include the zygote and embryonic cells up to the 16-cell stage. - Pluripotency: Embryonic stem cells that can differentiate into any embryonic cell type but not extra-embryonic cells. - Multipotency: Adult stem cells that have lost some potency. They can produce a limited range of cell types related to their tissue.
Adult Stem Cells - Small numbers remain in adults for growth, replacement, and repair in tissues like bone marrow, skin, gut, heart, and brain. - Example: Stem cells in bone marrow can only differentiate into blood cells (red blood cells, monocytes, neutrophils, and lymphocytes). - Stem Cell Therapy: Research involves introducing adult stem cells into damaged tissue to treat diseases like leukemia or injuries like skin burns.

Oncology: How Tumours Form

The Mechanism of Cancer - Cancers arise due to uncontrolled mitosis. - Cancerous cells divide repeatedly and uncontrollably to form a tumour (an irregular mass of cells).
Mutations and Oncogenes - Changes in genes that control cell division are called mutations. - A gene that causes cancer when mutated is an oncogene. - Most mutations lead to early cell death or destruction by the immune system. Cancerous cells evade these outcomes, passing the mutation to descendants.
Terminology and Classifications - Carcinogens: Agents that cause cancer (e.g., UV light, tar in tobacco smoke, X-rays, asbestos, and oncoviruses). - Benign Tumours: Tumours that do not spread from their original site (e.g., warts). - Malignant Tumours: Tumours that spread, invade, and destroy other tissues. They interfere with organ functions (blocking intestines, blood vessels, or lungs). - Metastasis: Malignant cells break off and travel through the blood or lymphatic system to form secondary growths. This is dangerous because secondary cancers are hard to detect and remove. - Detection: A typical tumour contains approximately $10^9$ (one thousand million) cancerous cells by the time it is detected.

Stages of Mitosis (PMAT)

Overview: Mitosis produces two genetically identical daughter nuclei with the same number of chromosomes as the parent. In humans, although the diploid number is $46$ , after the $S$ phase there are $92$ DNA molecules present (in the form of sister chromatids) before division.
1. Prophase - Chromosomes condense and become visible when stained. - Two identical sister chromatids are joined at the centromere. - Two centrosomes (replicated in $G_2$ ) move toward opposite poles of the nucleus. - Spindle fibres (protein microtubules) emerge from the centrosomes. - In animal cells, centrosomes consist of two centrioles. - The nuclear envelope breaks down into small vesicles.
2. Metaphase - Centrosomes reach opposite poles. - Spindle fibres continue to extend. - Chromosomes line up at the equator of the spindle (the metaphase plate), equidistant to the centrosome poles. - Spindle fibres attach to the centromeres of the chromosomes. - Each sister chromatid is attached to a fiber from an opposite pole.
3. Anaphase - The centromere divides in two, separating the sister chromatids. - Spindle fibres shorten. - Separated chromatids (now referred to as chromosomes) are pulled to opposite poles.
4. Telophase - Chromosomes arrive at opposite poles and begin to decondense. - Nuclear envelopes reform around each set of chromosomes. - Spindle fibres break down.

Practical: Observing Mitosis in Root Tips

Specimen Choice - Growth in plants happens in meristems. The root tip meristem (found just behind the root cap) is ideal. - Garlic or onion (Allium cepa) bulbs are used, encouraged to grow roots by suspension over water for $1$ to $2\,\text{weeks}$ .
The Squash Technique - Removal: Approximately $1\,\text{cm}$ of the root tip is removed. - Staining: Tips are placed in a stain such as warm, acidified acetic orcein, which stains chromosomes a deep purple. - Squashing: The stained tip is gently squashed on a glass slide using a blunt instrument (e.g., the handle of a mounting needle) to spread the cells into a thin sheet. - Analysis: Micrographs can be used to identify stages (P, M, A, or T) and create annotated drawings.