Cell Cycle and Replication

• The cell cycle is a sequence of events leading to cell division into two daughter cells, including growth, DNA replication, and division.

Cell Replication

• Cell replication is an asexual process where one parent cell produces two genetically identical daughter cells without DNA combination, resulting in clones.
• It is needed for growth, repair of old or damaged cells, and procreation in bacteria, archaea, protozoa, and some eukaryotes.

Cell Replication in Prokaryotes

• Prokaryotes reproduce through binary fission, a process simpler and faster than asexual reproduction in eukaryotes.
• Binary fission steps:
  • Replication of the circular DNA chromosome and cell elongation occur.
  • The two circular chromosomes migrate to opposite ends of the cell.
  • The cell membrane pinches in two, forming a septum (new cell wall) that extends and divides the cell into two.
• Bacterial binary fission can complete in about 20 minutes at room temperature, leading to exponential growth.

Cell Replication in Eukaryotes

• The cell cycle is more complex with multiple chromosomes unlike prokaryotes, which have one circular chromosome.
• The cell cycle has three distinct phases: interphase, mitosis, and cytokinesis.

Interphase

• DNA replication occurs during interphase; chromosomes are decondensed and distributed through the nucleus.
• Organelles like mitochondria and ribosomes replicate and divide.
• Interphase Stages:
  • G1 (gap 1) stage: Cell growth, increased cytosol, and synthesis of proteins needed for DNA replication; the cell commits to continuing the cycle or enters a non-dividing quiescent G0 stage (About 11 hours).
  • S (synthesis) stage: DNA is replicated, resulting in two identical copies of the original DNA (About 7 hours).
  • G2 (gap 2) stage: Further growth occurs, along with the synthesis of proteins, including spindle microtubules (About 4 hours).

Mitosis

• Marked by the appearance of chromosomes and the disappearance of the nuclear membrane.
• Stages of Mitosis:
  • Prophase: Chromosomes shorten and thicken, becoming visible as double-stranded structures; the spindle forms, and the nuclear membrane breaks down.
    • Prophase begins with chromatin and histone condensation into distinct chromosomes.
  • Metaphase: Double-stranded chromosomes align at the equator of the cell.
  • Anaphase: Sister chromatids separate and are pulled to opposite ends of the spindle through the contraction of spindle fibers.
  • Telophase: A nuclear membrane forms around each group of single-stranded chromosomes, which then decondense.
• Mitosis is a continuous process where stages identify key changes in chromosome appearance and position.

Cytokinesis

• Cytosol and organelles distribute around the new nuclei and are enclosed within a plasma membrane.
• Cytokinesis in Animal Cells:
  • The cytoplasm bridge between the nuclei narrows.
  • The plasma membrane pinches, separating nuclei and cytoplasm into two new cells.
• Cytokinesis in Plant Cells:
  • A cell plate forms between the chromosome groups.
  • The cell plate develops into a new cell wall for each new cell.
• Mitosis is essentially the same in both plant and animal cells.

Regulation of the Cell Cycle

• Checkpoints ensure a complete, damage-free genome copy is transmitted to daughter cells.
• The G1 checkpoint, occurring at the G1 stage of interphase, determines readiness for division.
• Damaged or incomplete DNA stops the cell cycle, leading to a non-dividing stage (G0) or destruction.
• p53, a tumor-suppressor protein, acts as the 'security guard' at the G1 checkpoint.
• Organelles, such as mitochondria and chloroplasts, must be replicated during interphase.

p53 Protein

• p53 repairs most mutations, preventing them from leading to cancer.
• During G1, tumor proteins (including p53) check for damaged DNA.
• If damaged DNA is detected, p53 activates a DNA repair system, stopping G1 until repair is complete.
• If damage is irreparable, apoptosis is initiated.
• A mutation in the gene that forms p53 causes syndromes that cause many cancers.

Proto-oncogenes

• Proto-oncogenes are genes that produce cells initiating the cell cycle and can be switched off to prevent excessive cell production.
• Mutations can turn proto-oncogenes into oncogenes, leading to excessive cell production or tumors.

Mutagens

• Mutagens cause or increase DNA mutations.
• Chemical mutations:
  • Carcinogens, such as tobacco smoke, can interrupt spindle formation, leading to cancers.
  • Teratogens, like thalidomide, can cause physical defects in embryos.
• Physical Mutagens:
  • UV light can cause DNA mutations and is thought to mutate p53.
• Biological Mutagens:
  • Viruses can carry oncogenes or insert their DNA into a tumor suppressor gene.

Programmed Cell Death

• A turnover state exists in body tissues where old cells die and new cells form.
• In adults, cell renewal rate equals cell death rate.
• DNA damage triggers apoptosis, a genetically controlled process of cell self-destruction.

Apoptosis

• Apoptosis eliminates:
  • Cells at the end of their natural life.
  • Dysfunctional, damaged, or diseased cells (including virus-infected cells or cells with irreparable issues detected during cell cycle checkpoints).
  • Excessive cells (e.g., to correct form digits in a human embryo).
• Mechanisms of Apoptosis
  • Intrinsic (internal) signal = Intrinsic Pathway:
    • Cell damage or stress leads to Bcl-2 proteins determining whether to protect the cell (pro-survival) or initiate apoptosis (pro-apoptotic).
    • Damage activates p53; significant damage results in cytochrome c leakage from the mitochondria.
    • Pro-apoptotic Bcl-2 proteins create pores in the mitochondria to release cytochrome c into the cell.
    • Cytochrome c combines with Apaf-1 to form an apoptosome, which activates a cascade of caspases to break down proteins within the cell.
  • The signal comes from inside the cell, activated by radiation, viral infection, toxins, or damaged DNA.
  • p53 leads to cytochrome c leakage from the mitochondria when DNA problems arise.
  • Bcl-2 proteins regulate this process, promoting (pro-) or inhibiting (anti-) apoptosis.
  • After the stress, Bcl-2 proteins form pores in the mitochondria, releasing cytochrome c into the cytoplasm.
  • Cytochrome c forms a complex with Apaf-1 (apoptotic protease-activating factor), creating an apoptosome that activates a cascade of caspases.
  • Caspases are proteins that are sequentially activated and break down proteins within the cell.
• Extrinsic (external) signal:
  • Death receptors, transmembrane proteins on the plasma membrane, bind to cytokine signaling molecules, initiating a caspase activation cascade and apoptosis.
• Both mechanisms lead to:
  • Cell shrinkage.
  • Formation of blebs (protrusions of the cell membrane).
  • Formation of apoptotic bodies.
  • Clean-up of apoptotic bodies via phagocytosis

Deviant Cell Behavior

• Psoriasis:
  • Is a chronic autoimmune condition where skin cells are overproduced, resulting in raised, inflamed skin patches.
• Cancer:
  • Occurs when the cell cycle becomes uncontrolled, leading to excessive reproduction and masses called tumors.
  • Malignant tumors, like melanomas, can spread throughout the body and establish secondary cancer sites.

Cell Differentiation

• Cell differentiation is when cells become specialized for a specific function.
• Gene expression is specialized, and cells lose their ability to reproduce.

Stem Cells

• Stem cells are undifferentiated cells.

Changes to turn a single-celled zygote into a newborn baby include:

- Many mitotic cell divisions increase the total number of cells to many billions.
- Cell differentiation occurs to produce over 200 different cell types.
- The organization of these differentiated cells into tissues, organs, and systems occurs.

Types of Stem Cells

- Totipotent
    - Can give rise to all cell types.
    - Includes the fertilized egg and early embryonic cells.
- Pluripotent
    - Cells of the primary germ layers (ectoderm, mesoderm, endoderm).
    - Stem cells from the inner cell mass of the embryonic blastocyst.
- Multipotent
    - The ability to differentiate into a closely related family of cells.
- Oligopotent
    - The ability to differentiate into a few cell types.
- Unipotent
    - The ability to produce only cells of their own type and can self-renew.

Types of Stem Cells

• Embryonic Stem Cells (ESCs):
  • Source: Inner cell mass of an early embryo (blastocyst stage).
  • Obtained from extra embryos created during IVF procedures.
  • Ethical concern: Extraction destroys the embryo.
  • Advantage: Pluripotent – can become any cell type.
  • Disadvantage: Cells aren’t matched to the patient.
• Parthenotes:
  • Source: Derived from unfertilized human eggs, artificially stimulated to begin development.
  • Limitation: Cannot develop into a human being.
• Adult Stem Cells (Somatic Stem Cells):
  • Source: Found in various body tissues (bone marrow, skin, blood, umbilical cord blood).
  • Potency: Multipotent – can become only certain types of cells.
  • Advantage: Patient’s own cells can be used → lower chance of rejection.
  • Disadvantage: Already partly specialized, may be difficult to obtain.

Basal Stem Cells of the Epidermis

• Location: Basal layer of the epidermis.
• Function: Undergo cell division → produce two daughter cells:
  • One remains a basal stem cell.
  • One differentiates into a keratinocyte → moves upwards, replaces old skin cells, and is eventually shed.
• Importance:
  • Enables skin regeneration and healing.
  • Contributes to the skin’s ability to recover from damage due to presence in epidermis & dermis.
• Intestinal Stem Cells:
  • The epithelial lining of the small intestine is regenerated every 4/5 days, replaced by new cells produced by stem cells.
• Haematopoietic Stem Cells:
  • Located in the bone marrow.
  • Divide to give rise to cells that differentiate into the various types of blood cells.

Binary Fission in a bacterial cell

• The first is cell elongation and replication, where the cell grows and DNA is replicated to create two circular chromosomes.
• The second stage is migration, where the two circular chromosomes move to either end of the cell.
• The third stage is separation, where a septum and a new cell wall forms to create 2 new cells.

Zygote definition

• Single cell formed when a sperm fertilizes an egg, beginning a new organism's development.