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Cell Cycle
8/31/11 First Lecture
15
Medical
Graduate
08/31/2011

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Term
What two fundamental processes must occur in mitosis?
Definition
1. Duplication of DNA and organelles

2. Division into daughter cells
Term
What are the 4 phases of the cell cycle and what major processes occur at each
Definition
1. G1 phase - Stage of growth and monitoring the environment
2. S phase - Synthesis of DNA
3. G2 - Second growth phase, mistakes in DNA replication are repaired
4. M - Mitosis, division into daughter cells
Term
What are the key principles involved in the cell cycle that all cells need to follow to successfully divide and survive?
Definition
1. Maintain a set sequence of steps
2. Ensure accurate duplication
3. Duplicate DNA only once
4. Divide only once
Term
What proteins regulate cell division?
Definition
Cyclin proteins bind to cyclin-dependent kinases which when found in high enough concentration control the progression of the cell through the cell cycle
Term
What is the name of the M-phase cyclin and how was it discovered?
Definition
MPF

Oocytes were injected with cytoplasm from M-phase cells and the oocyte was driven to M phase, but no driven into M phase when injected with interphase cytoplasm
Term
Explain the positive feedback loop associated with MPF
Definition
After the MPF cyclin binds to the MPF Cdk, it is primed but inactive (there are 2 phosphates bound to it at this point. An activating kinase must remove one). The active form decreases activity of an inhibitory kinase and increases the activity of the activating kinase, promoting more active MPF, leading to the MPF explosion
Term
Describe the process of Cdk degradation
Definition
Ubiquitin ligase binds to the E2E3 complex with E1's help. This complex passes the ubiquitin onto the lysine side chain of the Cdk and acts as a signal for the protein to be degraded.

Note: E3 provides protein specificity so the ubiquitin is passed to the correct target
Term
Give an example of MPF self regulation for degradation
Definition
Anaphase promoting complex (APC) serves as the complex that binds to the MPF and leaves the ubiquitin to signal it is ready for degradation. It is self regulation because the higher levels of MPF promote the production of APC
Term
What proteins control the transition from G1 into S phase?
Definition
Mitogens (growth factors) bind to the surface receptor of the cell and initiate a signal transduction pathway that initiates transition into S phase. After this, the cyclin's self promotion/degradation mechanism controls the rest of the cell cycle.

Note: This is the "point of no return" in the cell cycle
Term
Explain the process by which DNA replication is achieved through Cdk complexes
Definition
The G1-Cdk complex activates the E2F protein (via deactivation of Rb), which actives the transcription of essential S-phase genes. This leads to active forms of the S-Cdk, allowing the cell to enter S phase and undergo DNA replication
Term
How does S-Cdk regulate DNA replication?
Definition
The S-Cdk removes an inhibitory protein from the origin recognition complex, after which phosphorylation of the ORC initiates DNA replication.
Term
What are Cyclin-dependent kinase inhibitors?
Definition
CKIs proteins serve as breaks on the cell cycle by inactivating Cdk's to slow down the processes in each step

Note: Do not stop the cell cycle, only slow it
Term
What is G0 phase?
Definition
G0 phase is a semi-permanent state of cell cycle arrest that most cells exist in. CKI's play an important role in this.
Term
Give 2 examples of checkpoints in the cell cycle
Definition
1. One chromosome remains unattached to the kinetochore until all the others are attached, then attaches itself signaling the transition into anaphase

2. Damaged DNA actives transcription of the p21 mRNA which activates the expression of a CKI that rests the cell in S phase until repair is complete
Term
How does the loss of the cell cycle control lead to cancer?
Definition
Mutations in cell cycle regulation genes (ex. Rb) can lead to unregulated cell proliferation
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