Regulation of DNA Replication

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Presentation transcript:

Regulation of DNA Replication

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

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

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

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

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

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

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

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

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

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

Sister Chromatid Separation Securin inhibits separase Separase cleaves cohesin

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