Cell Division and Cycle Overview

Introduction

• New cells are needed for growth, replacement of damaged cells, and increasing the number of cells.
• Cells are formed using asexual reproduction where mitosis (eukaryotes) and binary fission (bacteria) are used to produce identical cells.
• Sexual reproduction combines two cells to create a new cell that is not identical to the parent cells.

Cell Division

• Prokaryotes: Have a single circular DNA molecule that replicates and attaches to the cell membrane.
• Eukaryotes: Division is triggered when a cell reaches an appropriate size and has enough protein and energy stores, to prevent the cell from becoming too large, making nutrient and waste exchange difficult.

Cell Cycle

• The cell cycle is a series of stages that occur from when a cell divides into two cells until those daughter cells divide as well.
• Includes:
  • Interphase:
    • G1 Phase: Cell grows in size, and increases its supply of proteins and organelles for division.
    • S Phase: DNA replicates, resulting in two sister chromatids per chromosome.
    • G2 Phase: Second growth phase, all structures needed for division are created, including centrioles, and protein, and organelle synthesis.
  • M Phase: Mitosis, or karyokinesis, where the nucleus divides. Occurs in eukaryotes only, some cells such as nerve and brain cells, do not undergo mitosis.
  • C Phase: Cytokinesis, the physical process of cell division where the cytoplasm divides into two daughter cells with the help of actin and myosin contractile rings that form a cleavage furrow.
• Mitosis:
  • Consists of four stages (PMAT):
    • Prophase: Chromatin condensates into chromosomes, the nucleolus and nuclear membrane disappear, and the mitotic spindle formation begins from centrioles.
    • Metaphase: Chromosomes attach to kinetochore fibers and line up along the cell equator.
    • Anaphase: Spindle fibers pull sister chromatids apart to opposite poles, each pole with a full set of original genes.
    • Telophase: Chromosomes reappear as chromatin, the nuclear envelope begins to form, the nucleolus is visible, and the spindle breaks apart.
• Cell division assists in growth, repair, and replacement of damaged cells within tissues.

Regulation of Cell Cycle

• Aims to control cell division to prevent uncontrolled cell division and tumor formation.
• Regulatory molecules: cyclins and cyclin-dependent kinases (CDK)
  • These molecules form a heterodimer that activates or deactivates target proteins through phosphorylation.
• Checkpoints ensure proper cell cycle progression:
  • G1 Checkpoint: Verifies that everything is ready for DNA replication.
  • G2 Checkpoint: Checks that the cell is ready for mitosis.
  • Metaphase Checkpoint: Ensures that the cell is ready to complete cell division.
• Loss of Cell Cycle Control leads to tumor formation.
  • A damaged or defective p53 gene causes a loss of information needed to respond to control signals. Cancer cells with faulty p53 lack responsiveness to cell cycle control signals, leading to uncontrolled cell division.
  • Normal Cells: DNA replicates correctly, chemical signals start and stop the cell cycle, cells communicate to prevent overcrowding.
  • Cancer Cells: DNA replicates with mutations, chemical signals for starting and stopping the cell cycle are ignored, cells don't communicate, leading to the formation of tumors.
• Cancer: Essentially a failure of cell division control.
  • All cancers require a shutdown of p53 activity, which plays a key role in the G1/S checkpoint and halts cell division if damaged DNA is detected.

Cell Death

• Necrosis: Unregulated cell death caused by disease, injury, or lack of blood supply.
• Apoptosis: Regulated cell death for the removal of unwanted cells. This is an energy-dependent process.
• Necrosis VS Apoptosis:
  • Necrosis is a massive, uncontrolled event, while apoptosis is a controlled, individual cell process.
  • Necrosis causes cell swelling, while apoptosis leads to cell shrinking.
  • Necrosis results in inflammation, whereas apoptosis prevents inflammation.
• Apoptosis in Physiological Situations:
  • About 100,000 cells are produced each second by mitosis, with a similar number dying by apoptosis.
  • Embryogenesis: Apoptosis plays a role in morphogenesis to eliminate excess cells, for example, between fingers and toes.
  • Metamorphosis: Apoptosis assists in the transformation of a tadpole into a frog.
• Apoptosis in Adults:
  • Tissue Remodeling: Apoptosis eliminates unwanted cells through tissue renewal. Example: the mammary glands.
  • Prostate Gland: Testosterone controls the level of apoptosis in the prostate gland.
• Apoptosis in Disease:
  • Too Much Apoptosis: Tissue atrophy, neurodegeneration.
  • Too Little Apoptosis: Hyperplasia, athersclerosis.