Exam 4 (3) Flashcards
3 Roles of G1 Cyclin-CDK
- Activate transcription of genes for proteins for DNA replication
- Assemble prereplication complexes at the origins (specific genomic regions where the replication starts)
- Activate G1-S and S-Phase Cyclins (S-phase are CKI Bound)
Role of G1-S Cyclins; What does this lead to?
Leads to the activation of the G1-S CDKs –> phosphorylate the CKI Bound S-phase Cyclins to begin S-phase transition
These CKIs are now able to recognized by SCF Ubiquitin Ligase –> Ubiquitin is covalently attached (polyubiquitination) –> Degraded by Proteosome
2 Roles of S-Phase Cyclins
- Activate DNA Replication Origins (specific genomic regions where the replication starts)
- Activate M-cyclins –> M-Cyclin CDK is inhibited by Wee1 Kinase for the time being
What happens to drive the G2 to M phase transition?
Cdc25 phosphatase activates the Mitotic Cyclin CDKs previously inhibited by Wee1 Kinase
The Early First 4 Roles of Mitotic Cyclin-CDKs (+ the technical name)
Technical Name: CyclinB-CDK1
- Phosphorylate Condensins –> Chromosome Condensation
- Phosphorylate Nuclear Lamin –> Nuclear Envelope Breakdown
- Phosphorylate Microtubule Associated Proteins –> Changes in MT Dynamics
- Phosphorylate ER + Golgi Associated Proteins –> Reorganization of ER + Golgi
Much Later 5th Role of Mitotic Cyclin-CDKs
Eventually promotes APC-Cdc20 Activity (Ubiquitin Ligase) –> Polyubiquitination + Degradation of Securin (protein that inhibits Separase) –> Release Separase –> Separase degrades Cohesins –> Chromatids Separate (Anaphase!!)
Upon sufficient separation, Cdc14 Phosphatase is activated –> redirects an APC to Mitotic Cyclins to polyubiquinate them –> Degradation of Mitotic Cyclins
This causes the first 4 effects to be reversed and M-phase is over
How do Checkpoints relate to Cyclins?
Checkpoints serve as negative feedback mechanisms that reverse changes; they inhibit Cyclin/CDK transition to block cell cycle progression when signaled to (ex. DNA damage, spindle fiber problems)