1. Cell Cycle, Mitosis, Meiosis Unit 5

2. Welcome Back!  Musical Chairs  TODAY:  Notes on Cell Cycle  Become medical school students on oncology rotation  Homework for next time: Watch Bozeman video on cell cycle, mitosis and meiosis. There *may* be a quiz.

3. Unit 5 Plan  AP Biology Essential Knowledge covered: In eukaryotes, heritable information is passed to the next generation via processes that include the cell cycle and mitosis or meiosis plus fertilization.  Day 1 – Cell Cycle & Case Study  Day 2 – Mitosis & Case Study  Day 3 – Meiosis & Modeling Activity  Day 4 – Modeling continued, Quiz over notes/Quizlet (online)

4. Why Care about Cell Cycle Control?  Lifetime Risk of Developing Cancer: Approximately _____ percent of men and women will be diagnosed with all cancer sites at some point during their lifetime?  In 2012, there were an estimated __________ people living with all cancer sites in the United States.

5. Why Care about Cell Cycle Control?  Lifetime Risk of Developing Cancer: Approximately 39.6 percent of men and women will be diagnosed with all cancer sites at some point during their lifetime?  In 2012, there were an estimated 13, 780,000 people living with all cancer sites in the United States.

6. Why Care about Cell Cycle Control? Oncologists – Study cancer and help those affected  Average salary in 2015 ~ $277,000 Time to become an oncologist? 10-13 years Bachelors, Medical School, Residency Demand? United States will likely face a 48% increase in demand for oncologist services by 2020—in large part because of the expected 81% increase in cancer survivorship and the 48% increase in cancer incidence caused by the aging of the population.

7. Day 1 – Cell Cycle  In eukaryotes, heritable information is passed to the next generation via processes that include the cell cycle and mitosis or meiosis plus fertilization.  So, passing on heritable information begins with the ability for cells to go through the cell cycle.  Why else is the cell cycle important?

8. Some Cell Cycle Basics The cell cycle is divided into Interphase and Mitotic (including mitosis & cytokinesis) Interphase consists of three phases: growth, synthesis of DNA, preparation for mitosis. Mitosis consists of prophase, metaphase, anaphase and telophase. Mitosis alternates with interphase in the cell cycle. Mitotic Phase

9. Cell division results in genetically identical cells

10. How do cells know when to divide? Cell communication signals  chemical signals in cytoplasm give cue  signals usually are proteins  activators  inhibitors Activation of cell division

11. Coordination of cell division  A multicellular organism needs to coordinate cell division across different tissues & organs  critical for normal growth, development & maintenance Do you think cells all have the same timing for their cell cycle? Discuss with a friend – think of an example.

12. G2G2 S G1G1 M metaphase prophase anaphase telophase interphase (G 1, S, G 2 phases) mitosis (M) cytokinesis (C) C  Frequency of cell division varies by cell type  embryo  cell cycle < 20 minute  skin cells  divide frequently throughout life  12-24 hours cycle  liver cells  retain ability to divide, but keep it in reserve  divide once every year or two  mature nerve cells & muscle cells  do not divide at all after maturity  permanently in G 0 Frequency of cell division

13. Cell Cycle – Think/Pair/Share  The cell cycle is a complex set of stages that is highly regulated with checkpoints, which determine the ultimate fate of the cell.  Why would it need to be highly regulated?  What might the checkpoints result in?

14. Overview of Cell Cycle Control  Two irreversible points in cell cycle  replication of genetic material  separation of sister chromatids  Checkpoints  process is assessed & possibly halted centromere sister chromatids single-stranded chromosomes double-stranded chromosomes There ’ s no turning back, now!

15. Checkpoint control system  Checkpoints  cell cycle controlled by STOP & GO chemical signals at critical points  signals indicate if key cellular processes have been completed correctly  3 major checkpoints:  G 1, G 2 and M

16. Checkpoint control system  3 major checkpoints:  G 1  can DNA synthesis begin?  G 2  has DNA synthesis been completed correctly?  commitment to mitosis  M  are all chromosomes attached to spindle?  can sister chromatids separate correctly?

17. G 1 Checkpoint is the most critical!  primary decision point  “restriction point”  if cell receives a “GO- ahead”signal, it will divide  if cell does not receive signal, it exits cycle & switches to G 0 phase

18. G 0 phase  G 0 phase  non-dividing, differentiated state  many human cells in G 0 phase  liver cells  in G 0, but can be “called back” to cell cycle by external cues  nerve & muscle cells  highly specialized  arrested in G 0 & can never divide

19. “Go-ahead” signals Protein molecules that promote cell growth & division  internal signals  “promoting factors”  external signals  “growth factors”  Primary mechanism of control  phosphorylation  Use of kinase enzymes  Which either activates or inactivates cell signals by adding a phosphate

20. Cell cycle Chemical signals  Cyclins (PROTEIN)  regulatory proteins  levels cycle in the cell  Cdk’s (ENZYME)  cyclin-dependent kinases  phosphorylates cellular proteins  activates or inactivates proteins  Cdk-cyclin complex  Forms MPF (mitosis promoting factor) complex  Triggers movement into next phase activated Cdk inactivated Cdk

21. Cdk / G 1 cyclin Cdk / G 2 cyclin (MPF) G2G2 S G1G1 C M G 2 checkpoint G 1 checkpoint Active Inactive Active Inactive Active mitosis cytokinesis MPF = Mitosis Promoting Factor Replication completed DNA integrity Chromosomes attached at metaphase plate M checkpoint Growth factors Nutritional state of cell Size of cell

22. Cyclin & Cyclin-dependent kinases (Cdk’s)  CDKs & cyclin drive cell from one phase to next in cell cycle  proper regulation of cell cycle is so key to life that the genes for these regulatory proteins have been highly conserved through evolution  the genes are basically the same in yeast, insects, plants & animals (including humans)

23. External signals Sometimes the signals are EXTERNAL… Growth factors  Proteins or steroid hormones that bind to receptors on the cell surface, with the primary result of activating cellular proliferation and/or differentiation.  Many growth factors are quite versatile, stimulating cellular division in numerous different cell types; while others are specific to a particular cell-type  Allow coordination between cells  density-dependent inhibition  crowded cells stop dividing  When not enough growth factor left to trigger division in any one cell, division stops  anchorage dependence  to divide cells must be attached to a substrate or tissue matrix  “touch sensor” receptors

24. Cancer & Cell Growth  Cancer is essentially a failure of cell division control  unrestrained, uncontrolled cell growth  What control is lost?  lose checkpoint stops  gene p53 plays a key role in G 1 restriction point  p53 protein halts cell division if it detects damaged DNA  options:  stimulates repair enzymes to fix DNA  forces cell into G 0 resting stage  keeps cell in G 1 arrest  causes apoptosis of damaged cell  ALL cancers have to shut down p53 activity p53 is the Cell Cycle Enforcer

25. Development of Cancer Cancer develops only after a cell experiences ~6 key mutations (“hits”)  unlimited growth  turn on growth promoter genes  ignore checkpoints  turn off tumor suppressor genes (p53)  escape apoptosis  turn off suicide genes  immortality = unlimited divisions  turn on chromosome maintenance genes  promotes blood vessel growth  turn on blood vessel growth genes  overcome anchor & density dependence  turn off touch-sensor gene It ’ s like an out of control car!

26. What causes these “hits”? Mutations in cells can be triggered by  UV radiation  chemical exposure  radiation exposure  heat  cigarette smoke  pollution  age  genetics

27. Tumors  Mass of abnormal cells  Benign tumor  abnormal cells remain at original site as a lump  p53 has halted cell divisions  most do not cause serious problems & can be removed by surgery  Malignant tumors  cells leave original site  carried by blood & lymph system to other tissues  start more tumors = metastasis  impair functions of organs throughout body

28. Traditional treatments for cancers Treatments target rapidly dividing cells  high-energy radiation  kills rapidly dividing cells  chemotherapy  stop DNA replication  stop mitosis & cytokinesis  stop blood vessel growth

29. Time for your oncology rotation!  You are medical school students on an oncology rotation  Choose a narrator, scribe and researcher  Start with the “Mystery” – when you have answered the questions, raise a hand for your supervisor to check in with you (yes, that is me)  You must check in with me before proceeding to each new portion of your case study.  Your group’s grades will be based on our discussions – everyone must be prepared to answer the supervisors questions!