To Divide or Not to Divide: Regulation of the Cell Cycle Shalini Nag David Shahbazian Elizabeth Morse

Learning Goals Students will understand: – cell division is essential to life and is a tightly regulated process in normal, healthy tissues. – uncontrolled cell division can lead to cancer due to a failure of cell cycle checkpoints.

Learning Objectives Students will be able to: 1.Describe the purpose(s) of regulated cell division and provide physiological examples. 2.Explain relationships among the parts of the cell cycle, including regulatory checkpoints. 3.Predict the fate of cells following various trying circumstances (e.g. injury, DNA damage).

Activity #1 Introduction to the Cell Cycle Class discussion & brainstorm

Why Do Cells Divide? Brainstorm about it! On your own, jot down a few of your ideas.

Why do cells divide?

When Do Cells Divide? Brainstorm about it! On your own, jot down a few of your ideas.

When do cells divide?

What do these physiological examples of cell division have in common? -Embryonic development -Cell replacement - Wound Healing They don’t occur all the time!  Regulation Normal, healthy cells only divide when they have received specific instructions (e.g. a chemical signal) indicating it is time to divide.

How is cell division regulated? The Cell Cycle A series of tightly regulated cellular events, including the duplication & division of genetic material and organelles, resulting in the production of two daughter cells.

Activity #2 Understanding the Goals, Parts & Regulation of the Cell Cycle Concept mapping

What does the cell cycle accomplish? 1) Growth – Cells must grow in size so that daughter cells are the same size as parental cells 2) Inheritance – Cells must pass on genetic information to daughter cells. As a result, prior to cell division, DNA (as well as cellular organelles) are replicated so that each daughter receives a copy.

Arrange the events of the cell cycle in order Growth in size Beginning of organelle duplication DNA synthesis Nuclear division/Mitosis Cell division/Cytokinesis

The Cell Cycle Growth in size Beginning of organelle duplication DNA synthesis Nuclear division/Mitosis Cell division/Cytokinesis

Cell Cycle Checkpoints Checkpoints are control mechanisms assessing successful completion and fidelity of certain steps in cell division cycle Checkpoints evaluate cell’s readiness to proceed to the next step of cell division and will pause cell division until detected mistakes are repaired Irreparable mistakes detected by checkpoints will lead to cell death Failure of checkpoints may accelerate cell replication, lead to mutations and result in cancer

Where are the major checkpoints?

Activity #3 Determining Cell Fate Matching exercise & think-pair-share

Determining Cell Fate Each of you has been provided with a sheet of paper that has certain scenarios listed in the left column and some cell responses in the right column. Please take 2-3 minutes to consider the various scenarios and match what you think would be the cell’s response to them.

What will happen when…Cells will… 1. A healthy tissue is injured?A. Enter regulated cell division. 2. Healthy cells stop receiving signals to divide? B. Begin unregulated cell division. 3. Interphase checkpoint of cells is damaged, i.e. they can divide without a specific signal? C. Undergo regulated cell death (apoptosis). 4. A healthy cell makes an error during DNA replication? D. Enter resting phase. 5. A healthy cell has irreparable DNA damage? E. Pause division to repair damage. 6. The DNA damage checkpoint fails? F. None of the above.

Think-Pair-Share In groups of 2 or 3 please compare your responses and discuss any differences. You have 3 minutes.

What will happen when…Cells will… 1. A healthy tissue is injured?A. Enter regulated cell division. 2. Healthy cells stop receiving signals to divide? B. Begin unregulated cell division. 3. Interphase checkpoint of cells is damaged, i.e. they can divide without a specific signal? C. Undergo regulated cell death (apoptosis). 4. A healthy cell makes an error during DNA replication? D. Enter resting phase. 5. A healthy cell has irreparable DNA damage? E. Pause division to repair damage. 6. The DNA damage checkpoint fails? F. None of the above.

Unregulated Cell Division & Cancer With your group, discuss the following questions 1.How many of the given examples do you think are likely to result in cancer? 2.What is the common feature in these examples? 3.If you had to explain in one sentence, what causes cancer, what would you say? You have 3 minutes

To Divide or Not to Divide: Summary 1.Cell division is essential to life, required for cellular and organismal growth, development & response to injury. 2.The transitions between stages of the cell cycle are carefully regulated by cellular checkpoints. 3.The fate of cells varies following stresses, such as injury or DNA damage. Cells that sustain checkpoint damage may enter unregulated cell division, leading to cancer.

Beginning of organelle duplication Growth in size DNA synthesis Nuclear division/ Mitosis Cell division/ Cytokinesis X

What will happen when…Cells will… 1. A healthy tissue is injured?A. Enter regulated cell division. 2. Healthy cells stop receiving signals to divide? B. Begin unregulated cell division. 3. Interphase checkpoint of cells is damaged, i.e. they can divide without a specific signal? C. Undergo regulated cell death (apoptosis). 4. A healthy cell makes an error during DNA replication? D. Enter resting phase. 5. A healthy cell has irreparable DNA damage? E. Pause division to repair damage. 6. The DNA damage checkpoint fails? F. None of the above.