1. Cell Cycle Regulation Chapter 12 12.3 – Pt. 1 Pgs. 238-243 Objective: I can describe and how the cell cycle is regulated and controlled to occur at certain times and at certain speeds.

2. Cytoplasmic Signals (Transduction Pathways) Used to think event of previous phase signals next phase  Example: DNA replicates (S)  G2 Found signals in cytoplasm cause a phase (proven by experiments)

3. Regulation of the Cell Cycle Checkpoints exist in different phases  If cell OK, allowed to go to next phase  Checkpoints NOT at end of phase Where are checkpoints? Cell Cycle Control System

4. G1 Checkpoint (Example)

5. Checkpoints (more details coming…leave space…?) G 1 checkpoint – near end of G 1 (restriction point)  Checks if cell grew enough? DNA damaged?  If not, will put into G 0 (rest period) OR will activate apoptosis (cell suicide) G 2 checkpoint – near end of G 2  Checks if DNA replicated OK in S; enough organelles? M checkpoint – at Metaphase of Mitosis  Checks if chromosomes lined up correctly, so that each cell gets all the DNA they need (homologous pairs, singled, etc.) All controlled by regulation molecules…

6. Regulation Molecules (main ones) Cyclin(s) = (class of proteins)  Concentration levels will cycle (high to low)  Acts as an activator for… Cdk(s): Cyclin Dependent Kinase(s) = (class)  Phosphorylates “things”(other molecules)  Activated by cyclin No cyclin = inactive Cdk Cyclin + Cdk = MPF (Maturation-Promoting Factor)  No cyclin = no MPF activity

7. Cell Cycle Clock (Details of G2 checkpoint) Concentration of cyclin increases: causes… S phase  G2 phase Cyclin binds to Cdk  forms MPF complex Causes Mitosis to occur (passes G2 chckpt.) In Anaphase, cyclin is degraded in MPF Concentration of cylin drops: causes… Mitosis to end  enter G1 phase http://highered.mheducation.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/free/0072437316/120082/bio34a.swf::Control%20of%20the%20Cell%20Cycle

8. Details of M Checkpoint If kinetochore not attached to spindle, sends signal molecule. Signal molecule activates protein. Protein (cohesin) keeps sister chromatids attached to each other… When kinetochore attached to spindle, stops sending signal molecule. Protein inactivates. Sister chromatids can now separate.

9. Details of G1 Checkpoint Regulated by Cdks & cyclins, but also controlled by a very special protein called  p53 (made by gene p53) Specifically checks if DNA damaged  If damaged, p53 signals other enzymes to repair it and forces cell to go into G 0  If too badly damaged, p53 starts apoptosis

10. External Signals for Cell Division Growth Factors – drive cell division  Ex. PDGF (Platelet-Derived Growth Factor) Allows tissue to repair

11. Other Factors Control Cell Division Density-Dependent Inhibition  If cells crowded, stop dividing Based on molecules, not physical contact Anchorage Dependence  Cells only divide if anchored

12. Cell Regulation Game http://nobelprize.org/educational_game s/medicine/2001/cellcycle.html http://nobelprize.org/educational_game s/medicine/2001/cellcycle.html Play this game to understand the cell cycle better!