2. AP Biology Regulation of Cell Division

3. AP Biology 1.Coordination of cell division a. A multicellular organism needs to coordinate cell division across different tissues & organs i. critical for normal growth, development & maintenance a. coordinate timing of cell division b. coordinate rates of cell division c. not all cells can have the same cell cycle 2

4. AP Biology G2G2 S G1G1 M metaphase prophase anaphase telophase interphase (G 1, S, G 2 phases) mitosis (M) cytokinesis (C) C a. Frequency of cell division varies by cell type i. embryo i. cell cycle < 20 minute ii. skin cells i. divide frequently throughout life ii. 12-24 hours cycle iii. liver cells i. retain ability to divide, but keep it in reserve ii. divide once every year or two iv. mature nerve cells & muscle cells i. do not divide at all after maturity ii. permanently in G 0 2. Frequency of cell division 3

5. AP Biology 3. Overview of Cell Cycle Control a. Two irreversible points in cell cycle i. replication of genetic material ii. separation of sister chromatids b. Checkpoints i. process is assessed & possibly halted centromere sister chromatids single-stranded chromosomes double-stranded chromosomes There ’ s no turning back, now! 4

6. AP Biology 4. Checkpoint control system a. 3 major checkpoints: i. G 1 /S 1. can DNA synthesis begin? ii. G 2 /M 1. has DNA synthesis been completed correctly? 2. commitment to mitosis iii. spindle checkpoint 1. are all chromosomes attached to spindle? 2. can sister chromatids separate correctly? 5

7. AP Biology 5. G 0 phase a. If signal is “NO” cell goes to G 0 phase: b. G 0 phase 1. non-dividing, differentiated state 2. most human cells in G 0 phase i. liver cells a. in G 0, but can be “called back” to cell cycle by external cues ii. nerve & muscle cells a. highly specialized b. arrested in G 0 & can never divide 6

8. AP Biology a. How do cells know when to divide? i. cell communication signals a. chemical signals in cytoplasm give cue b. signals usually mean proteins 1. activators 2. inhibitors 6. Activation of cell division experimental evidence: Can you explain this? 7

9. AP Biology 7. Cyclin & Cyclin-dependent kinases a. CDKs & cyclin drive cell from one phase to next in cell cycle 1. proper regulation of cell cycle is so key to life that the genes for these regulatory proteins have been highly conserved through evolution 2. the genes are basically the same in yeast, insects, plants & animals (including humans) 8

10. AP Biology 8. External signals a. Growth factors 1. coordination between cells 2. protein signals released by body cells that stimulate other cells to divide a. density-dependent inhibition I. crowded cells stop dividing II. each cell binds a bit of growth factor a. not enough activator left to trigger division in any one cell b. anchorage dependence I. to divide cells must be attached to a substrate a. “touch sensor” receptors 9

11. AP Biology 9. Cancer & Cell Growth a. Cancer is essentially a failure of cell division control i. unrestrained, uncontrolled cell growth b. What control is lost? i. lose checkpoint stops ii. gene p53 plays a key role in G 1 /S restriction point a. p53 protein halts cell division if it detects damaged DNA 1. options: a. stimulates repair enzymes to fix DNA b. forces cell into G 0 resting stage c. keeps cell in G 1 arrest d. causes apoptosis of damaged cell b. ALL cancers have to shut down p53 activity p53 discovered at Stony Brook by Dr. Arnold Levine p53 is the Cell Cycle Enforcer 10

12. AP Biology 10. Development of Cancer a. Cancer develops only after a cell experiences ~6 key mutations (“hits”) i. unlimited growth i. turn on growth promoter genes ii. ignore checkpoints i. turn off tumor suppressor genes (p53) iii. escape apoptosis i. turn off suicide genes iv. immortality = unlimited divisions i. turn on chromosome maintenance genes v. promotes blood vessel growth i. turn on blood vessel growth genes vi. overcome anchor & density dependence i. turn off touch-sensor gene It ’ s like an out-of-control car with many systems failing! 11

13. AP Biology 11. What causes these “hits”? a. Mutations in cells can be triggered by  UV radiation  chemical exposure  radiation exposure  heat  cigarette smoke  pollution  age  genetics 12

14. AP Biology 12. Tumors a. Mass of abnormal cells 1. Benign tumor 1. abnormal cells remain at original site as a lump 1. p53 has halted cell divisions 2. most do not cause serious problems & can be removed by surgery 2. Malignant tumor  cells leave original site  lose attachment to nearby cells  carried by blood & lymph system to other tissues  start more tumors = metastasis  impair functions of organs throughout body 13

15. AP Biology 13. Traditional treatments for cancers a. Treatments target rapidly dividing cells i. high-energy radiation 1. kills rapidly dividing cells ii. chemotherapy 1. stop DNA replication 2. stop mitosis & cytokinesis 3. stop blood vessel growth 14

16. AP Biology Any Questions??