1. Cyclins G1 cyclin (cyclin D) S-phase cyclins (cyclins E and A) mitotic cyclins (cyclins B and A) Cyclin-dependent kinases (Cdks)kinases G1 Cdk (Cdk4) S-phase Cdk ((Cdk2) M-phase Cdk (Cdk1 Proteins in the Cytoplasm Affect Cell Cycle Control

2. Cyclins cycle!!!

3. The M Phase Promoting Factor Function and Composition –Composed of Cdk 1 and cyclins A or B –Rises when E cyclin is destroyed during G2 –Assembly of mitotic spindle –Breakdown of nuclear envelope –Condensation of the chromosomes –Phosphorylates histones, nuclear filaments and microtubule associated proteins that form the spindle –Promotes the degredation of G2 cyclin (Interesting) –Homework: –Investigate the function and composition of the G1 cyclin (cyclin D) and Cdk (Cdk4) as well as the S-phase promoting factor (cyclin E and A and Cdk 2).

4. Other proteins control the cycle as well----APC (cyclosome) Allows sister chromatids to separate by triggering destruction of cohesins Destroys cyclin B by ubiquinating it Turns on G1 cyclin for the next cycle Degrades geminin, a protein which prevents DNA replication

5. Cell cycle game http://nobelprize.org/educational_games/m edicine/2001/cellcycle.htmlhttp://nobelprize.org/educational_games/m edicine/2001/cellcycle.html http://www.bama.ua.edu/~hsmithso/class/ bsc_495/spindle/spindle_web.htmlhttp://www.bama.ua.edu/~hsmithso/class/ bsc_495/spindle/spindle_web.html

6. Other proteins monitor the cell cycle for lethal mistakes G0

7. Checkpoints G1

8. checkpoints 1. DNA damage checkpoints a. G1 checkpoint-Damage inhibits cdk2 until DNA is repaired or cell enters apoptosis b. G2 checkpoint -Check for completion of DNA synthesis by monitoring Okasaki fragments. 2. Spindle checkpoints a. check all kinetochores for attachment to spindles. Checkpoints require proteins.

9. Guardians of the Genome p53 -senses DNA damage and halt progression of the cell cycle. It is a tumor supressor gene. Mutations in p53 are recessive. Over 50% of all cancers have mutant p53. ATM (ataxia telangiectasia mutated) -detects double stranded breaks in DNA. Maintains telomere length. MAD (mitotic arrest deficient) - binds a kinetochore until a spindle connects. If no spindle attaches, entry into anaphase is blocked by inhibiting APC. Mutations in MAD produce aneuploidy.