1. Javad Jamshidi Fasa University of Medical Sciences The Eukaryotic Cell Cycle

2. An ordered series of events leading to cell replication

3. Control of cell division is vital

4. Cells should divide where and when needed Nearly identical proteins regulate in all eukaryotes

5. Cell cycle

6. 2 key molecular processes in the cell cycle

7. The progression of cell cycle stages is the same for all eukaryotes Rapidly replicating human cells the full cell cycle in about 24 hours G1 takes 9 hours The S phase 10 hours G2, 4.5 hours Mitosis 30 minutes 90 minutes in rapidly growing yeast cells. Only 8 minutes in early embryonic development of the fruit fly

8. The master controllers of the cell cycle Protein kinases that contain a: Regulatory subunit (cyclin) Catalytic subunit (cyclin-dependent kinase, or CDK)

9. Regulate the activities of multiple proteins involved in: Entry into the cell cycle DNA replication Mitosis By phosphorylating them at specific regulatory sites Activating some Inhibiting others

10. Only active when bound to a regulatory cyclin subunit Different types of cyclin-CDK complexes initiate different event G1 CDKs and G1/S phase CDKs promote entry into the cell cycle S phase CDKs trigger S phase Mitotic CDKs initiate the events of mitosis Multiple mechanisms are in place to ensure that the different CDKs are only active in the specific stages of the cell cycle.

11. Cyclins bind to and activate CDKs, define their activity and substrate specificity Cyclins are only present during the cell cycle stage that they trigger and are absent in other cell cycle stages. Cyclins not only regulate a particular cell cycle stage but also prepare for the next cell cycle stage.

12. Cell cycle events must occur in the proper order These oscillations in CDK activity are a fundamental aspect of eukaryotic cell cycle control Positive feedbacks Negative feedbacks The surveillance mechanisms which called checkpoint pathways

14. CDKCyclinFunctionGeneral Name CDK1 Cyclin A and B MitosisMitotic CDKs CDK2 Cyclin E and A Entry into the cell cycle S phase G/S phase CDKs S phase CDKs CDK4 and CDK6 Cyclin D G1 Entry into the cell cycle G1 CDKs

16. Kinases and Phosphatases CAK kinase Wee1 kinase Cdc25 phosphatase Inhibitory Proteins p27 INK4 Rb Ubiquitin-Protein Ligases SCF APC/C

21. Control of the G1-S phase transition Growth Factor

24. Eukaryotic chromosomes are replicated from multiple replication origins No eukaryotic origin initiates more than once per S phase S phase continues until replication from all origins along the length of each chromosome are Complete

29. Meiosis phases