1. Cell Cycle Stages cells pass through from 1 cell division to the next

2. In order for cell to divide, 4 events must occur…  Reproductive signal  DNA replication  Segregation of chromosomes  Cytokinesis

3. Comparing Pro- and Eukaryotes:  Prokaryotes: Cell division = reproduction of the organism Reproductive signal usu. triggered by external factors  Eukaryotes Cell division can = reproduction of organism Multicellular eukaryotes also use for growth and repair of tissue Signals for division relate to needs of entire organism

4. 2 Main Phases of Cell Cycle:  Interphase Active metabolism Synthesizes needed materials No cell division  M phase Mitosis cytokinesis

5. Interphase has 3 key stages:  G 1 phase Growth Normal metabolism Cells that are not dividing become arrested here and enter G 0  S phase DNA replication Synthesis of histones  G 2 phase Final prep for division (protein synthesis)

7. Internal Control of Cell Cycle  Under optimal conditions, length of eukaryotic cell cycle is constant for given cell type  Regulatory molecules control cell cycle Genetically programmed in nucleus Trigger specific events

8. Cell Cycle Checkpoints  Control Cell Division  Genetically programmed to ensure that the events of one stage of cell cycle is complete before next begins

9. Cell Cycle Checkpoints:  1 st – most important – restriction point Late in G 1 Ensures cell is large enough  G 2 -M checkpoint – makes sure replication is complete  Metaphase checkpoint – chromosomes properly attached to spindle  http://www.cellsalive.com/cell_cycle.htm http://www.cellsalive.com/cell_cycle.htm  http://nobelprize.org/educational_games/medicine/2001/cellcycle.html http://nobelprize.org/educational_games/medicine/2001/cellcycle.html

10. Regulation of Cell Cycle  Length of cell cycle varies with organisms and type of cells  Regulatory molecules in eukaryotes control cell cycle: Cyclin-dependent kinases (CDKs) – activate or deactivate other proteins by phosphorylating them Cyclins  Regulatory proteins  Bind to Cdks to turn them on  Levels fluctuate predictably during cell cycle

11. Regulation, cont.  Specific cyclin binds to specific CDK, forming cyclin-CDK complex Turns enzymes on/off by phosphorylating them  Ex. p27 Protein that inhibits cell division When phosphorylated p27 degrades and cell can divide

12. 4 Major Cyclin-CDK Complexes  G 1 -CDK – prepares cell to pass from G 1 to S phase  G 1 /S-CDK – commits the cell to replication  S-CDK – initiates replication  M-CDK Promotes mitosis Activates APC

13. External Control of Cell Cycle  Certain drugs can stop cell cycle at specific checkpoint  Hormones Plants – cytokines Animals – steroids and protein hormones  Density of cells Crowding regulates cell division

14. Cancer  Cells lack normal inhibitions Large # of cells undergoing mitosis Reduced contact inhibition Reduced dependence on growth factors Apparently unlimited # of generations  Cancer cells have unique characteristics Nucleus makes up large portion of cell May lose traits of original cell Genetically unstable  Duplications, deletions, rearrangements of chromosomes

15. Cancer as a Multi-Step Process  Altered expression of specific genes Normal genes mutate into cancer-causing genes  Proto-oncogenes  oncogenes Overactive growth-promoting pathways  Tumor suppressor genes Block cell division

16. Back-Up Systems  DNA repair system  Apoptosis  Telomeres  For cancer to develop, mutations triggering cancer have to occur and the body’s natural back-ups fail