Biology Lecture Notes: Cell Cycle, Mitosis, and Cancer

Sexual Reproduction, Biodiversity, and Evolution

• Mechanism of Biodiversity: Sexual reproduction increases biodiversity by combining genetic material from two distinct parents. This process involves genetic recombination, which ensures that offspring possess unique genetic combinations different from their parents and siblings.

• Driving Evolution: Genetic recombination fuels the evolutionary process through three primary mechanisms:

  • Introduction of Genetic Variation: It creates a diverse pool of traits within a population.

  • Survival Advantage: Increased variation enhances the probability that some individuals will possess traits allowing them to survive significant environmental changes.

  • Natural Selection: Evolutionary adaptation is driven over time as natural selection acts upon this inherent variation, favoring traits that confer a survival or reproductive advantage.

The Eukaryotic Cell Cycle

• Definition of the Cell Cycle: The orderly sequence of stages that takes place between the time a eukaryotic cell divides and the time the resulting daughter cells also divide.

• Interphase: This is the period of the cell cycle where the cell spends the majority of its time (three out of the four stages). It consists of:

  • $G_1$ Phase (Gap 1): The cell undergoes physical growth, accumulates materials for DNA synthesis, and performs its normal metabolic functions. The cell also checks the environment to ensure conditions are suitable for replication.

  • S Phase (Synthesis): DNA replication occurs during this phase. Each chromosome is duplicated, resulting in two sister chromatids. At the end of this stage, the genetic material has been doubled.

  • $G_2$ Phase (Gap 2): The cell continues to grow and synthesizes the proteins necessary for cell division, such as those that form the spindle fibers. It also performs a final check on the duplicated chromosomes for any errors or damage.

• M Phase (Mitotic Phase): This phase encompasses both nuclear division (mitosis) and the division of the cytoplasm (cytokinesis).

Detailed Phases of Mitosis (PMAT)

• Chromosomal Structures and Terminology:

  • Histone: A group of proteins that form the nucleosome structure of eukaryotic chromatin.

  • Nucleosome: A structural unit of a eukaryotic nucleus consisting of a length of DNA coiled around a core of histones; resembles a "string of beads."

  • Chromatin: The network of DNA strands and associated proteins found within the nucleus.

  • Chromosome: The condensed, organized structure of DNA and protein that carries genetic material from parent to child cell.

  • Chromatid: A single DNA double helix; after replication, two identical sister chromatids are joined at the centromere.

  • Centromere: The constricted region on a chromosome that joins sister chromatids and ensures accurate separation during division.

  • Kinetochore: A complex assembly of proteins located at the centromere that serves as the attachment point for spindle fibers.

  • Centrosome: The primary microtubule-organizing center of the cell.

  • Centriole: A cell structure in animal cells that helps organize the mitotic spindle.

• The Phases of Mitosis:

  • Prophase: This is the longest phase of mitosis. The chromatin condenses into visible chromosomes. Each chromosome consists of two sister chromatids joined at a centromere. The nuclear envelope begins to disintegrate. The mitotic spindle begins to form as centrioles move toward opposite poles. Astral rays (microtubules) extend from the centrioles to form the aster, which aids in positioning the spindle fibers.

  • Prometaphase: The nuclear envelope fully dissolves. Spindle fibers attach to the kinetochores of the chromosomes. The chromosomes begin their movement toward the center of the cell.

  • Metaphase: The chromosomes align perfectly at the cell's equatorial plane, known as the metaphase plate. The spindle apparatus is fully formed, and each chromosome is tethered to spindle fibers from opposite poles via kinetochores.

  • Anaphase: This is the shortest phase of mitosis. The centromeres split, and sister chromatids (now individual chromosomes) are pulled toward opposite poles. This movement is driven by the shortening of the spindle fibers.

  • Telophase: Chromosomes reach the poles and begin to de-condense back into less-dense chromatin. New nuclear envelopes reform around each set of daughter chromosomes. The spindle apparatus breaks down.

Cytokinesis: Animal vs. Plant Cells

• Cytokinesis in Animals: This process involves the formation of a cleavage furrow, an indentation that appears after anaphase. A contractile ring composed of actin filaments forms and tightens, pinching the cell membrane in the middle until the parent cell is split into two separate daughter cells.

• Cytokinesis in Plants: Because plant cells possess rigid cell walls, they cannot pinch in half. Instead, a cell plate is formed in the center of the cell. Actin filaments guide vesicles filled with cell wall materials to the center. These vesicles fuse to create a new plasma membrane and cell plate, which eventually develops into a new, rigid cell wall for the daughter cells.

Cell Cycle Regulation and Checkpoints

• Definition of Cell Division: The process by which a parent cell divides into two daughter cells, comprising mitosis (nuclear division) and cytokinesis (cytoplasmic division).

• Regulatory Checkpoints:

  • $G_1$ Checkpoint: Assesses DNA for damage. If damage is detected, the cell may enter apoptosis (programmed cell death). It also ensures the cell has sufficient nutrients and growth signals to proceed to replication.

  • $G_2$ Checkpoint: Verifies that DNA replication is complete and checks for any remaining DNA damage before the cell enters mitosis.

  • M Checkpoint: Occurs during metaphase; verifies that all chromosomes are correctly aligned on the metaphase plate and that spindle fibers are properly attached to ensure accurate distribution of genetic material.

The Genetics and Molecular Basis of Cancer

• Apoptosis: Planned or programmed cell death that occurs when a cell is abnormal, infected by a virus, or damaged. It is a critical defense mechanism against the spread of viruses, tumor growth, and cancer.

• Regulatory Genes:

  • Proto-oncogenes (The "On Switches"): Normal genes that promote cell division. Cyclins are a primary example; they regulate the timing and progression of the cycle. When mutated, proto-oncogenes become oncogenes (cancer-causing genes), which lead to uncontrolled division and may stop apoptosis.

  • Tumor Suppressor Genes (The "Off Switches"): Normal genes that slow the cell cycle, repair DNA, or promote apoptosis if the cell is mutated. Mutations in these genes cause them to lose their inhibitory function.

• Notable Proteins:

  • p53 (The "Guardian of the Genome"): Activated by DNA damage (via radiation or chemicals). It binds to DNA to trigger repair genes. If the damage is irreparable, it initiates apoptosis. Mutations in p53 lead to the accumulation of mutations and uncontrolled cell growth.

  • p27: Regulates the cycle by inhibiting cyclin-dependent kinases (Cdks), preventing the cell from entering the S phase prematurely.

  • Cyclins and Cdks: Cyclins activate Cdks (Cyclin-dependent kinases), which act as a "phosphate key" to control transitions between cell cycle phases.

Characteristics of Cancer Cells

1. Uncontrolled Division: Cancer cells divide indefinitely due to mutations in regulation, ignoring the controlled limits of normal cells.

2. Lack of Differentiation: They do not contribute to specific tissue functions and can reproduce an infinite number of times.

3. Abnormal Nuclei: Their nuclei are often oversized and contain an abnormal number of chromosomes, including deletions or extra genes.

4. Evasion of Apoptosis: They ignore signals for programmed cell death, even when severely damaged.

5. Insensitivity to Growth Signals: They bypass external cues that typically regulate growth.

6. Tumor Formation: They lose contact inhibition, continuing to divide and pile up into masses called tumors.

7. Metastasis and Angiostasis:

   • Metastasis: The process by which cancer cells invade nearby tissues, enter the bloodstream or lymphatic system, and colonize distant organs to form secondary tumors.

   • Angiostasis/Angiogenesis: Cancer cells create enzymes and signals to stimulate the growth of new blood vessels to supply the tumor with nutrients.

Specialized Cellular Contexts

• Stem Cells: Cells that retain the ability to divide and are used by the body to repair injuries. Example: Red bone marrow stem cells, which reproduce to become various types of blood cells.

• Therapeutic vs. Reproductive Cloning: Therapeutic cloning provides insight into cell and tissue simplicity, allowing for the study of reproductive cloning through efficient, understandable models.

• Binary Fission: The method of reproduction in prokaryotic cells (bacteria). The cell separates using a cell wall and plasma membrane to produce two daughter cells.

Questions & Discussion

• How is sexual reproduction related to biodiversity and evolution?

  • It introduces variation through genetic recombination, providing the raw material for natural selection and environmental adaptation.

• What type of cells undergo mitosis and why is it important that the number of chromosomes remains constant?

  • Somatic (body) cells undergo mitosis. Constancy is required so that each daughter cell is genetically identical to the parent cell, maintaining the organism's functional integrity.

• Describe how meiosis results in the formation of haploid cells.

  • Meiosis involves two rounds of division that reduce the chromosome number by half, specifically for the production of gametes.

• Why is meiosis important to fertilization? What is a zygote?

  • Meiosis ensures that when two gametes fuse, the resulting zygote (a fertilized egg) has the correct diploid number of chromosomes.

• What are the three checkpoints and what do they check for?

  • $G_1$ (DNA damage/nutrients), $G_2$ (DNA replication completion), and M (chromosome alignment).