Cell Division and Reproduction

Introduction

• New cells are needed for growth, repair, and replacement of damaged cells.
• New cells are produced by two different types of reproduction: asexual reproduction and sexual reproduction.
• Asexual reproduction: one cell divides into two identical cells; examples include mitosis (in eukaryotes) and binary fission (in bacteria).
• Sexual reproduction: two cells (an egg and a sperm) are joined to produce a new cell (zygote) that is not identical to the parent cells; example is meiosis.

Cell Division

• Prokaryotes (Binary fission):
  • Prokaryotes have a single circular DNA molecule.
  • This DNA molecule replicates and each copy is attached to the cell membrane at different positions.
  • The cell pulls apart, separating the replicated and original DNA molecules.
  • Two identical daughter cells are formed.
• Eukaryotic Cells:
  • Cell division occurs when there is a need for new cells (growth, damage, etc.)
  • When a cell grows too large, nutrient and waste exchange becomes difficult.
  • The division process starts when the cell reaches the appropriate size and has enough protein and energy (ATP) stores.

Cell Cycle

• Represents the different stages from the moment a cell is divided into two distinct daughter cells until they are dividing themselves into new cells.
• Divided into three phases: G1, S, G2, and M.
• Interphase (G1, S, and G2 phases):
  • G1 (Primary Growth Phase):
    • Cell grows to appropriate size for division.
    • Increases its supply of proteins needed for division and number of organelles like mitochondria and ribosomes.
  • S (Synthesis Phase):
    • DNA amount doubles.
    • Chromosomes replicate, forming two sister chromatids.
  • G2 (Secondary Growth Phase):
    • 2nd growth phase after DNA duplication.
    • All cell structures needed for division are made (e.g., centrioles).
    • Proteins and organelles needed for division are synthesized.
• M (Mitosis) Phase:
  • Division of the nucleus.
  • Happens only in eukaryotes.
  • Some cells, like nerve and brain cells, do NOT undergo mitosis.
• C (Cytokinesis) Phase:
  • The physical process of cell division that divides the cytoplasm of a parental cell into two daughter cells.
  • After mitosis, the cytoplasm of the newly formed cells is separated by the aid of actin and myosin contractile ring, which forms a cleavage furrow.

Mitosis Stages

• Prophase:
  • Chromatin condenses into chromosomes.
  • Nucleolus and nuclear membrane disappear.
  • Mitotic spindle forms from centrioles.
• Metaphase:
  • Chromosomes attached to kinetochore fibers are lined up along the cell equator.
  • Each pole has a whole set of original genes.
• Anaphase:
  • Spindle fibers pull sister chromatids apart at their centromeres.
• Telophase:
  • Chromosomes reappear as chromatin (uncondensed).
  • Nuclear envelope starts to form.
  • Nucleolus is visible.
  • Spindle breaks apart.

Regulation of Cell Cycle

• Aims to control cell cycle to prevent uncontrolled division of cells.
• Regulatory molecules involved are called cyclins and cyclin-dependent kinases (CDK).
• Cyclin (regulatory subunit) and CDK (catalytic subunit) form a heterodimer that phosphorylates and activates or deactivates target proteins.
• Checkpoints of Cell Cycle are used to monitor and regulate the progress of the cell cycle, ensuring necessary processes are completed and DNA damage is repaired.
  • G1 Checkpoint: Ensures everything is ready for DNA replication.
  • G2 Checkpoint: Ensures the cell is ready for mitosis.
  • Metaphase Checkpoint: Ensures the cell is ready to complete cell division.

Uncontrolled Cell Cycle: Tumor Formation

• Uncontrolled cell division is a hallmark of tumor formation.
• A damaged/defective p53 gene causes loss of information needed to respond to control signals.
• Cancer cells with defective p53 do not respond to cell cycle controlling signals, resulting in uncontrolled division.

Normal Cell vs. Cancer Cell

• Normal Cell:
  • DNA is replicated properly.
  • Chemical signals start and stop the cell cycle.
  • Cells communicate with each other to prevent overcrowding.
• Cancer Cell:
  • Mutations occur in the DNA when it is replicated.
  • Chemical signals that start and stop the cell cycle are ignored.
  • Cells do not communicate with each other, leading to tumor formation.

Cancer: Failure of Cell Division Control

• Cancer is essentially a failure of cell division control, causing unrestrained, uncontrolled tissue growth.
• p53 gene plays a key role in the G1/S checkpoint.
  • p53 protein halts cell division if it detects damaged DNA.
  • All cancers have to shut down p53 activity.

Cell Death

• Necrosis (Unregulated Cell Death): Death of most or all of the cells in an organ or tissue due to disease, injury, or failure of the blood supply.
• Apoptosis (Regulated Cell Death): An energy-dependent programmed cell death for removal of unwanted individual cells.

Necrosis vs. Apoptosis

• Necrosis involves swelling of the cell and rupture of the cell membrane, releasing cellular contents into the surrounding area, potentially causing inflammation.
• Apoptosis involves a cascade of cellular events that lead to the dismantling of the cell without releasing cellular contents, minimizing inflammation or damage to surrounding cells.

Apoptosis in Physiologic Situations

• About 100,000 cells are produced every second by mitosis and a similar number die by apoptosis in the human body.
• Apoptosis during Embryogenesis:
  • Morphogenesis (Eliminates excess cells): Removal of unnecessary cells between fingers and toes.
• Apoptosis during Metamorphosis:
  • Eliminates cells no longer needed as an organism undergoes a change in form (example: tadpole to frog).

Apoptosis in Adults

• Tissue Remodeling (eliminates cells no longer needed):
  • Virgin Mammary Gland: Apoptosis occurs during late pregnancy and lactation and again during involution (when the gland returns to its non-pregnant state).
  • Prostate Gland: Apoptosis is regulated by testosterone levels.

Apoptosis and Disease

• Too Much Apoptosis:
  • Tissue Atrophy: Diminished size and function of an organ or tissue due to loss of cells.
  • Neurodegeneration: Progressive loss of structure and function of neurons, leading to neurological disorders.
• Too Little Apoptosis:
  • Hyperplasia: Abnormal increase in the number of cells in an organ or tissue.
  • Athersclerosis: Buildup of plaque in arteries, often leading to heart disease.