Eukaryotic Cell Cycle and Division

Eukaryotic Cell Cycle

• Eukaryotic cells have a definite nucleus, enclosed by a nuclear envelope.
• Cells divide to replace dead or missing cells via a regulated sequence of events.
• Division is stimulated by growth factors and inhibited by growth suppressors.
• Cell division timing varies by cell type, from every 30 minutes for embryonic cells to every 3 months for blood cells.
• Abnormal cell division can lead to cancer (too frequent) or cell death (apoptosis, not enough).

Cell Division Processes

• The eukaryotic cell cycle consists of two main phases:
  • Interphase: The cell is not dividing and preparing for mitosis.
  • Mitotic Phase (M): The cell divides, with replicated genetic material distributed to two daughter cells.
• Interphase is further divided into three sub-phases:
  • G₁: First gap phase, where the cell accumulates building blocks for DNA, proteins, and energy reserves.
  • S: Synthesis phase, where DNA replicates, creating an exact copy of each chromosome, resulting in sister chromatids attached at the centromere.
  • G₂: Second gap phase, where the cell replenishes energy, synthesizes proteins needed for chromosome manipulation, duplicates organelles, and prepares for the mitotic spindle.
• Mitosis is further divided into five sub-phases:
  • Prophase: Chromosomes condense, spindle fibers form from centrosomes, and the nuclear envelope breaks down.
  • Prometaphase: Chromosomes condense further, kinetochores appear at the centromeres, and spindle microtubules attach to them.
  • Metaphase: Chromosomes line up at the metaphase plate, with each sister chromatid attached to a spindle fiber originating from opposite poles.
  • Anaphase: Centromeres split, separating sister chromatids (now called chromosomes) and pulling them towards opposite poles. Spindle fibers elongate the cell.
  • Telophase: Chromosomes arrive at opposite poles, decondense, and are enveloped by new nuclear membranes. The mitotic spindle breaks down, and spindle fibers continue pushing poles apart.

G₁-Phase

• The first gap phase of interphase, where the cell is not actively dividing, but is preparing.
• Biochemical events during G₁ involve:
  • Semi-condensed chromosomes, forming nucleosomes and chromatin fibers.
  • Regulation by positive (growth factors) and negative (growth suppressors) regulators of growth and division.
• p53 is a key regulator that inhibits the cycle in G₁. If mutated, it can lead to loss of control and potentially cancer.

S-Phase (DNA Replication)

• The synthesis phase of interphase, where DNA is replicated.
• DNA remains in the semi-condensed chromatin structure formed during G₁.
• Replication requires various enzymes:
  • DNA topoisomerase relaxes supercoiled DNA by temporarily cutting the backbone of one or both DNA strands.
  • Helicases unwind the DNA double strands to create replication forks.
  • DNA polymerases synthesize sister chromatids for each chromosome using complementary base pairing (A-T and G-C).
• This results in the cell having twice the amount of DNA needed.

G₂-Phase

• The second gap phase of interphase, where the cell completes final preparations.
• It involves replenishing energy stores, synthesizing proteins needed for mitosis, duplicating organelles, and preparing resources for the mitotic spindle.

M-Phase & Cytokinesis

• Mitosis and cytokinesis involve:
  • Mitosis: The process of dividing the nucleus and chromosomes into two identical daughter nuclei.
  • Cytokinesis: The division of the cytoplasm, forming two daughter cells.
• Mitosis occurs in five phases, as described above.
• Cytokinesis differs for animal and plant cells:
  • Animal cells: A cleavage furrow separates the daughter cells.
  • Plant cells: A cell plate forms, eventually becoming a new cell wall between daughter cells.

Mitosis Gone Wrong

• Errors during mitosis can lead to:
  • Aneuploidy: Cells with extra or missing chromosomes, which can result in syndromes, cancers (e.g. Down Syndrome, leukemia).
  • Chromosome damage: Breaks, deletions, inversions, or translocations due to errors in separation.

Cancer

• Uncontrolled cell growth is a hallmark of cancer.
• Tumors are clusters of cancerous cells undergoing uncontrolled mitosis.
• If cancerous cells spread to other locations, it's called metastasis.
• Cancerous cells exhibit different traits like uncontrolled mitosis, faster growth, and abnormal structure.

Cancer Treatment

• Treatment approaches include:
  • Fixing the problem: E.g., bone marrow transplants.
  • Creating problems for cancerous cells: Interfering with mitosis via various medications and therapies.

Questions

• The eukaryotic cell cycle consists of Interphase, which prepares the cell for division, and the Mitotic Phase, where the cell divides.
• The G₁ checkpoint ensures the cell has the necessary building blocks for DNA replication, protein synthesis, and energy reserves.
• The M checkpoint ensures that chromosomes are correctly aligned at the metaphase plate before proceeding to anaphase.
• The eukaryotic cell cycle is crucial for growth, development, and repair of organisms.
• The text highlights the importance of understanding the cell cycle for developing effective cancer treatments.