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    4. Balanced growth and division G1 and G2 Balanced growth and division G1 and G2

    30. I will now quickly summarize the commonly accepted pathways in the G1-S transition …backwards, from the time the DNA duplex is about to open up for replication. Budding yeast: formation of pre-replication complex; the activation of the helicase activity of some components of the MCM complex is believed to indicate the start origin “firing”. Entry into S phase requires gene expression esp. those of S-phase genes; dotted arrows mean transcription; the E2F/DP transcription factors take center stage here…targets are parts of the pre-RC, Cdc7, cyclin E, A, Cdc25A. E2F activity inhibited by cycA/cdk2 (phosphor’n of DP…); cycA/cdk2 phosphorylates part of pre-RC (Cdc6) perhaps to prevent re-replication. Rb binds E2F and inhibits the latter’s transcrip activity. Rb inhibited by hyperphosphor’n carried out by Cdk2, Cdk4… Growth factor stimulation upregulates cycD synthesis and then cdk4 activation. p27Kip1, p21 (not shown)… note c-myc trans fac… Note positive and negative feedback loops…esp. cdc25A-CDK2, p27-CDK2. note: qualitative networkI will now quickly summarize the commonly accepted pathways in the G1-S transition …backwards, from the time the DNA duplex is about to open up for replication. Budding yeast: formation of pre-replication complex; the activation of the helicase activity of some components of the MCM complex is believed to indicate the start origin “firing”. Entry into S phase requires gene expression esp. those of S-phase genes; dotted arrows mean transcription; the E2F/DP transcription factors take center stage here…targets are parts of the pre-RC, Cdc7, cyclin E, A, Cdc25A. E2F activity inhibited by cycA/cdk2 (phosphor’n of DP…); cycA/cdk2 phosphorylates part of pre-RC (Cdc6) perhaps to prevent re-replication. Rb binds E2F and inhibits the latter’s transcrip activity. Rb inhibited by hyperphosphor’n carried out by Cdk2, Cdk4… Growth factor stimulation upregulates cycD synthesis and then cdk4 activation. p27Kip1, p21 (not shown)… note c-myc trans fac… Note positive and negative feedback loops…esp. cdc25A-CDK2, p27-CDK2. note: qualitative network

    37. Effect of p27Kip1 level on E2F and CycE/cdk2

    38. Simulation of the Restriction Point (CDK2 activation)

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