1. Regulation of DNA Replication

2. Control of the Cell Cycle
-The proteins that control the cell cycle are different from the proteins that are involved in the process
-Series of checkpoints
-Each checkpoint serves as a biochemical switch

3. Cyclin-Cdk Complexes APC/C Anaphase-Promoting Complex, or Cyclosome
G1-cyclin
APC/C Anaphase-Promoting Complex, or Cyclosome
-Regulated by protein destruction

4. Key Control Components
1. Cyclin-dependent kinases (Cdk)
-Activities vary throughout the cell cycle
-The targets of phosphorylation then varies
2. Cyclins
-Control the activity of Cdk’s
-Undergo synthesis and degradation in
each cell cycle
Cycling of the cyclins creates the cycles of the cyclin/Cdk complex allowing for the varying activities resulting in progression through the cell cycle

5. Control of Proteolysis of APC/C
-Degrading S and M-cyclins stops the Cdk activity and the Cdk’s targets become dephosphorylated and inactive
or Cdh1
or S-cyclin
-APC/C is active in G1 keeping Cdks inactive

6. S phase -Functions -Duplicate the DNA
-Protein packing must be reproduced
-2 issues facing DNA replication
-Accuracy of replication
-Copy DNA only once

7. Control of DNA Duplication
2 steps in Replication
1. Late M/Early G1
-Formation of prereplicative complex (pre-RC)
2. Start of S phase
-Preinitiation complex

8. Initiation of DNA Replication
ORCs are always bound to the origins
pre-RC assembly:
-Inhibited by Cdk
activity
-Stimulated by
APC/C

9. Initiation of DNA Replication
-S-Cdk triggers the preinitiation complex
-ORC and Cdc6 is P by Cdk
-Diassembly of pre-RC
-Cdc6 is degraded
-Cdt1 is inhibited by geminin

10. Initiation of DNA Replication
-DNA Replication is completed
-In late M, APC/C the degradation of geminin
-Cdk activity is decreased, OCRs are dephosphorylated
-Cdc6 is synthesized
-pre-RC assembly

11. Cohesins and Sister Chromatids
-Cohesin – large protein complex which holds the sister chromatids together
Smc (Structural Maintenance of Chromosomes)

12. Sister Chromatid Separation
Securin inhibits separase
Separase cleaves cohesin