In this activity, we will work with the two groups of genes that control the cell cycle, proto-oncogenes and tumor suppressor genes. We will also add a new group of genes that are in charge of the maintenance of our DNA, or the DNA repair system. Every cell's DNA is under constant attack from chemicals or radiation they are exposed to in the environment as well as chemicals that are the result of their own chemical reactions. DNA even becomes damaged during replication. ( more detail about DNA damage) This system detects and repairs the errors in the DNA. There is a chance however, that the genes that are involved in the DNA repair system may get damaged themselves. This can lead to an increase in the mutation rate for that cell and a greater possibility that you will accumulate the mutations needed to cause cancer. For this activity, we will assume that we are focusing in on our own skin cells.
REMEMBER:
Proto-oncogenes are like the gas peddle of the cell cycle. They produce proteins that signal a cell to divide. Some cells divide often (those found in an embryo or a wound healing) and would use this gene frequently, while others divide less frequently or not at all (muscle cell, neuron). If this gene were to mutate in such a way that it continually signals a cell to divide and we start accumulating too many cells, it is now an oncogene, and could be thought of as a gas peddle stuck in the down position.
Tumor Suppressor Genes are like the brake peddle of the cell cycle. When DNA is damaged, the tumor suppressor gene will stop the cell cycle so that repairs can be made. If the damage is beyond repair, it will signal the cell to commit suicide, apoptosis. This prevents the replication of cells with mutated DNA or cells that do not have a complete set of functioning genes, which are needed to maintain healthy cells. Cells die everyday and go unnoticed. We have probably all experienced massive apoptosis or cell suicide however, when our skin peels following a sunburn.
(This activity is done as a skit in front of the class to introduce new genes as well as review the students understanding of genes they have worked with previously. In this activity we will introduce the students to the genes involved in the DNA repair system or the genes in charge of maintenance. They will also work with the genes from the previous activity, proto-oncogenes and tumor suppressor genes, as they apply what they know to this new situation involving the interaction of more than one gene to produce a phenotype.)
WHO: One student will represent each of the following groups of genes (Wear sign or hat with the name of the group of genes they represent). Proto-oncogenes, tumor suppressor genes, DNA repair system, DNA synthesis system. The teacher or group leader will act as UV Radiation when needed.
WHAT: They will model the Cell Cycle
WHERE: They will represent the genes in a skin cell at the base of the stratified squamous tissue that is going through its cell cycle.
WHEN: Summer Vacation
WHY: The cell needs to replace cells that are lost during the normal activity of this person.
HOW: That is the job of each of these groups of genes working together. See their job descriptions below.
Proto-oncogenes
· Gas peddle of the cell cycle
· Produce protein that signals a cell to divide (hold up "Divide" sign)DNA Synthesis System
· Duplicate DNA so we have two sets of DNA when the cell divides (copy message decided by teachers onto card in 5 seconds with pencil)Tumor Suppressor Genes
· Brake peddle of cell cycle
· When DNA is damaged you stop the cell cycle to allow for repairs (hold up stop sign)
· If beyond repair (DNA repair system can't repair in 5 seconds) - signal cell to commit suicide (hold up apoptosis sign)
· If it is repaired (in 5 sec) the cell continues cycle (hold up GO sign)
· Prevents the replication of cells with damaged DNADNA repair system
· Maintenance for cell cycle
· Every cells DNA is under constant attack - chemicals, radiation, chemicals from own reactions (free radicals)
· Detects and repairs errors - even oncogenes and Tumor Suppressors (use eraser and pencil and repair within 5 sec.)
PROCEDURE FOR SKIT
Using your knowledge of how the cell cycle genes function, predict a possible outcome for your skin cells in each of the 8 combinations represented on the genetic wheel . Be sure to explain WHY you have arrived at this prediction. To use a genetic wheel you begin in the middle and work out passing through each layer selecting different gene combinations as you go. Each of the 8 locations on the outside of the wheel represents a different combination of the three genes. For example, if you begin in the center and select "proto-oncogene" in the first circle, "tumor suppressor gene" in the second circle, and "DNA repair" in the third circle you have the combination of genes we started with. All genes are functioning normally and the outcome should be normal cells. As a second combination, you could start in the middle and select "oncogene" in the first circle, "tumor suppressor gene" in the second circle, and "DNA repair" in the third circle. This would be the combination we described in the skit that resulted in too many normal cells, representing a benign tumor in our model.
Work through a few combinations as a class or in groups to be sure you know how to use a genetic wheel. Work through the remaining combinations on the genetic wheel on your own as homework.
To see how scientists will be able to determine which genes are functioning in a given cell in your body, such as a tumor, go to Genetic Variation and check out the Microarray section.
Remember, this is just a simple model that allows you to see how genes work together to produce a final outcome. In reality, each of these genes represents groups of genes that work together, along with others not included here, to move our cells through their cell cycle. Also, all the mutations needed to cause cancer, must occur in the same cell and that is why it usually takes time for cancer to develop and why it appears later in life.