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23 Cards in this Set

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When does DNA Replication occurr?
During the S Phase of Interphase.
Interphase = ?
M Phase = ?
Interphase = G1, S, G2
M-Phase = Mitosis & Cytokinesis
What occurrs during the G1 Checkpoint?
ensures cell is large enough to divide
What occurrs during the G2 Checkpoint?
unreplicated or damaged DNA stops cycle before entering mitosis
What occurrs during the M Checkpoint?
ensures that all chromosomes are correctly attached to spindle before separation of sister chromatids occurs; if it is not, then APC activation is blocked
T/F: Both cyclin and cdk concentrations fluctuate during the cell cycle.
False. Cdk's are always present. They are activated by cyclins, which are synthesized and degraded.
Functions of:
A) G1 Cyclins
B) G1/S Cyclins
C) S Cyclins
D) M Cyclins
A) G1 cyclins promote passage thorugh start or restriction point in late G1

B) G1/S cylins bind Cdks at end of G1 and commit cell to S phase

C) S cyclins bind cdks during S phase and are required for DNA replication

D) M cyclins promote mitotic events
A) G1 Cyclin AKA & binds cdk#:
B) G1/S AKA & binds cdk#:
C) S AKA & binds cdk#:
D) M AKA & binds cdk#:
A) G1 = D & cdk 4,6
B) G1/S = E & cdk 2
C) S = A & cdk 2
D) M = B & cdk 1
Describe the interaction between cyclin and its cdk, and how phosphorylation affects this interaction.
1. When cyclin binds to its cdk, it is a weak interaction.
2. One phosphate on the cdk makes it active. A second phosphate makes it inactive. Cdk Activating Kinase (CAK) is responsible for placing the activating kinase on cdk. A phosphotase takes off the inhibitor kinase. This results in a completely active cyclin/cdk complex.
What is p27?
p27 is an example of an inhibitory protein that binds to active cyclin/cdk complex. p21 also acts similarly.

*These reactions f(x) to pause the cell cycle.
How do we remove an inhibitory protein (i.e. p27) from the cyclin/cdk complex?
1. p27 is phosphorylated.
2. an active SCF puts on a multiubiquitin chain on p27 (w/ help of E1/E2)
3. this signals the protein to degradation via proteosome
How is cyclin degraded?
1. Inactive APC joins with its activating subunit.
2. The active complex puts a multiubiquitin chain on the cyclin (w/ help of E1/E2)
3. The cyclin is sent to the proteosome.
When a S Phase nucleus is fused with a G2 nucleus, the G2 cell stays in G2, while the S phase cell continues on with DNA Replication. Why?
Because the cell cycle is a unidirectional process that only occurs once.
What is the effect of hydroxyurea on the cell cycle?
It halts the cell cycle in S Phase, inhibiting DNA synthesis.
What is the effect of caffeine on the cell cycle?
It bypasses the G2 checkpoint, and when combined with hydroxyurea, results in catastrophe and suicidal mitosis.
Explain the positive feedback/amplification loop of m-cdk.
M-cdk can increase activation of cdc-25 (a phosphotase) by phosphorylating it to its active form. Cdc-25 is now active and activates the inactive cyclin/cdk by removing the inhibitory phosphate.
What are some functions of m-cdk during mitosis?
1. induces assembly of mitotic spindle and ensures the replicated hromosomes attach to the spindle.

2. It may also trigger chromosome condensation, nuclear envelope breakdown, and actin cytoskeleton rearrangement.
APC is a ubiquitin ligase. What is its function during the separation of sister chromatids?
1. Cohesins are the proteins that hold together the sister chromatids.

2. Separase is the proteosome that degrades cohesins, and is inactive when bound to securin.

3. Active APC targets securin for degradation.

4. Separase is now free to degrade cohesin connections between sister chromatids.

5. Anaphase occurrs. (APC = Anaphase Promoting Complex)
What is Rb and how does it work?
Rb is a tumor suppressor protein that when bound to E2F, inhibits S phase gene transcription and thus DNA synthesis.
Which part of the cell cycle is most often disrupted in cancer cells?
G1 to S Transition
Describe the effects of p53.
1. In undamaged cells, p53 interacts with a ubiquitin ligase in a very unstable manner.

2. DNA damage activates kinases that "P" and stabilize p53, and inhibit its interaction with the ubiquitin ligase.

3. p53 now binds to regulatory region of p21 gene.

4. Transcription and translation of p21 occur. p21 is a cdk inhibitor protein.

5. p21 can then bind to and inhibit G1/S and S cdks.

6. The cell cycle is halted so that DNA repair can occurr.

*mutations in p53 are prevalent in cancers (>50%)
How do the drugs methotrexate and 5-flurouracil operate?
They are anticancer drugs that damage DNA in S Phase so that it will not undergo division.
How do the drugs paclitaxel, vincristine, vinblastine, and colchicine affect the cell cycle?
They are anticancer drugs that stop the cell cycle at the M-Phase by inhibiting MT formation, and thus, inhibits pulling away of sister chromatids.