Warm-up 1. Place the following terms in order as they occur: prometaphase, G2, telophase, prophase, anaphase, G1, metaphase, S, and cytokinesis. 2. Answer the following questions using the phases found in the cell cycle that are mentioned in question 1.  Nucleus begins to fragment  DNA is being synthesized  Phase where chromosomes become visible  Cells split into two  Chromosomes line up in center  Centered on growth  Centromeres are dissolved  Spindle fibers begin assembly  The spindle fibers attach to the kinetochore of the chromosomes Write question and answer in notes.

In the early 1970s, a variety of experiments led to the hypothesis that the cell cycle is driven by specific signaling molecules present in the cytoplasm. Experiment 1 Experiment 2 S SS G1G1 G1G1 M MM EXPERIMENT RESULTS When a cell in the S phase was fused with a cell in G 1, the G 1 nucleus immediately entered the S phase—DNA was synthesized. When a cell in the M phase was fused with a cell in G 1, the G 1 nucleus immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.

Cell Cycle Control  Cell cycle control system: a cyclically operating set of molecules in the cell that both triggers and coordinates key events in the cell cycle.  The cell cycle is regulated at certain checkpoints by both internal and external signals.  A checkpoint is a control point in the cell cycle where stop and go-ahead signals can regulate the cycle.

Cyclins and Cyclin- Dependent Kinases  Cell cycle regulatory molecules are mainly proteins of two types: kinases and cyclins.  Kinases are enzymes that activate or inactivate other proteins by phosphorylating them.  Most cell cycle kinases stay at a constant concentration in the cell.  Cell cycle cyclins have fluctuating concentrations in the cell.  To be active, cell cycle kinases must be attached to a cyclin (cyclin-dependent kinase or Cdk).

MPF as a Cdk

Internal Checkpoints ProteinLocationPurpose Ras cyclinG1 checkpointChecks that cells are big enough to enter the next part of cell cycle. P53G1 checkpointInspects chromosomes for damage. ATM/NibrinS checkpointInspects copied DNA for mistakes. MPFG2 checkpointPhosphorylates proteins, which initiates mitosis. MAD1MetaphaseChecks that spindle fibers are attached to chromatids.

External Checkpoints  Growth factor: protein releases by certain cells that stimulates other cells to divide.  Density-dependent inhibition: crowded cells stop dividing.  Binding of a cell-surface protein to an adjoining cell sends a cell division-inhibiting signal.  Anchorage dependence: cells must be attached to substratum to divide.

Loss of Cell Cycle Controls in Cancer Cells  Cancer cells do not stop dividing when growth factors are depleted.  Hypothesis: cancer cells do not need growth factors in their culture medium to grow.  Hypothesis: cancer cells have an abnormal cell cycle control system.  The underlying basis of the abnormality is almost always a change in one or more genes that alters the function of their protein products, resulting in faulty cell cycle control. HeLa cells (green microtubles and orange Golgi)

 If and when cancer cells stop dividing, they do so at random points in the cycle.  Cancer cells can go on dividing indefinitely in culture if they are given a continual supply of nutrients.  Immortality.  Cells the acquire the ability to divide indefinitely are said to have undergone transformation.  Cancer cells evade the normal controls that trigger a cell to undergo apoptosis when something is wrong.

Why does cancer happen? Proto-oncogenes  Stimulate cell division  Oncogenes: mutated versions that are always “on.”

Tumor Suppressor Genes  Inhibit cell division.  “The brake pedal.”  Mutated versions always “off.”

p53 Mutation  Controls G1 phase; tells cell to kill itself (apoptosis) if DNA damage cannot be repaired.  Prevents development of mutated cells.  Mutation in gene allows cancer cells to continue dividing.

How does cancer happen?  Benign tumor: abnormal cells remain at the original site because they have too few genetic and cellular changes to survive at another site.  Malignant tumor: cells whose genetic and cellular changes enable them to spread to new tissues and impair functions of one or more organs. Breast cancer cell

Glandular tissue Tumor Lymph vessel Blood vessel Cancer cell Metastatic tumor A tumor grows from a single cancer cell. Cancer cells invade neighboring tissue. Cancer cells spread through lymph and blood vessels to other parts of the body. Cancer cells may survive and establish a new tumor in another part of the body.