Module 4 Flashcards

(48 cards)

1
Q

What are the main stages of the cell cycle?

A

G1, S, G2, M.

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2
Q

Why is the cell cycle unidirectional?

A

Ensures cells move forward without reversing.

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3
Q

How does the cell cycle contribute to development and tissue renewal?

A

Allows for growth, replication, and division of cells.

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4
Q

What role do Cyclin-Dependent Kinases (CDKs) play in the cell cycle?

A

Drive transitions through cell cycle phases by phosphorylating proteins, regulated by cyclins.

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5
Q

Which cyclin/CDK complexes are important at each cell cycle stage?

A

G1: Cyclin D/CDK4,6; S: Cyclin E/CDK2; G2: Cyclin A/CDK2; M: Cyclin B/CDK1.

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6
Q

What is the function of cyclin D/CDK4/6 during the G1 phase?

A

Promotes progression through G1 by phosphorylating Rb protein.

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7
Q

What is the role of cyclin E/CDK2 at the G1/S transition?

A

Drives the cell past the G1 checkpoint into the S phase.

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8
Q

How does cyclin A/CDK2 regulate the S and G2 phases?

A

Involved in DNA replication and preparation for mitosis.

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9
Q

How does cyclin B/CDK1 regulate the G2/M transition?

A

Triggers mitosis by promoting chromosome condensation, nuclear envelope breakdown, and spindle formation.

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10
Q

What are CDK activity thresholds, and why are they important?

A

CDK activity must reach thresholds for transitions (G1/S, S/G2, G2/M), ensuring proper timing.

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11
Q

What are cell cycle checkpoints, and how do they function?

A

Inhibit CDKs to stop the cycle until DNA damage is repaired or key processes are completed.

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12
Q

How do checkpoints respond to DNA damage?

A

Inhibit CDKs, allowing time for DNA repair.

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13
Q

What is the G1 checkpoint, and what does it ensure?

A

Ensures adequate size, nutrients, and undamaged DNA before entering S phase.

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14
Q

How does the G2 checkpoint contribute to cell cycle regulation?

A

Verifies DNA replication is complete and checks for damage before mitosis.

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15
Q

What is the spindle assembly checkpoint (SAC) and its importance?

A

Ensures all chromosomes are attached to spindle fibers before anaphase, preventing missegregation.

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16
Q

How do checkpoint kinases inhibit CDK activity?

A

ATM and ATR phosphorylate checkpoint proteins that inhibit CDKs, preventing progression until conditions are favorable.

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17
Q

How do cyclin levels fluctuate during the cell cycle?

A

Cyclin levels rise and fall cyclically, regulating CDK activity.

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18
Q

What is the role of the restriction point (R point) in the cell cycle?

A

Determines if the cell commits to the cycle and proceeds independently of growth signals.

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19
Q

How do cells ensure the completion of DNA replication before mitosis?

A

Checkpoints, especially G2, verify DNA replication is complete and undamaged.

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20
Q

What is the significance of cyclin degradation in the cell cycle?

A

Irreversible degradation ensures unidirectional progression by regulating CDK activity.

21
Q

How do cell cycle checkpoints contribute to genomic stability?

A

Prevent division of cells with damaged DNA or incomplete processes, protecting against instability and malignancies.

22
Q

What mechanisms control the degradation of cyclins?

A

Ubiquitin-mediated proteolysis targets cyclins for destruction by the proteasome.

23
Q

Why is the unidirectional nature of the cell cycle important?

A

Ensures cells move forward through stages without reversing, maintaining order and function.

24
Q

How does the Kinase Translocation Reporter (KTR) measure CDK2 activity?

A

Quantifies CDK2 activity by observing the translocation of CDK2 substrates, aiding in understanding regulation at the G1/S transition.

25
What is the importance of the G1/S transition checkpoint?
Ensures the cell is ready for DNA replication, confirming preparations and favorable conditions.
26
What happens at the G2/M transition checkpoint?
Checks for DNA damage and confirms replication is complete, ensuring readiness for mitosis.
27
Why is cell division important?
Development, reproduction, and cancer prevention.
28
What are the stages of the cell cycle?
G1, S, G2, M.
29
What is the role of CDKs in the cell cycle?
Drive transitions through phases; regulated by cyclins.
30
Which cyclin/CDK complexes are important at each cell cycle stage?
G1: Cyclin D/CDK4,6; S: Cyclin E/CDK2; G2: Cyclin A/CDK2; M: Cyclin B/CDK1.
31
What are CDK thresholds and why are they important?
Required for transitions (G1/S, S/G2, G2/M); ensure proper timing.
32
What are cell cycle checkpoints?
Inhibit CDKs until DNA damage is repaired or key processes are completed.
33
How does CDK regulation contribute to cancer?
Disruption leads to uncontrolled proliferation.
34
How does increased CDK activity promote cancer?
Increases cell proliferation via overexpression of Cyclin D/E.
35
How do mutations affect CDK inhibitors in cancer?
Inactivates CDK inhibitors, leading to uncontrolled cell cycle progression.
36
How is CCNE1 (Cyclin E1) related to cancer?
Amplified in various cancers, promoting cell cycle progression.
37
What is the role of FBXW7 in cancer?
Tumor suppressor; degrades Cyclin E; mutations increase Cyclin E levels.
38
How do chemotherapies target cancer cells?
Target DNA replication (replication fork stress).
39
What are CDK4/6 inhibitors used for?
Treat ER+ breast cancer.
40
What causes resistance to CDK4/6 inhibitors?
CDK2 activation, p16 inactivation, CDK4/6 overexpression, loss of ER, autophagy.
41
What are new strategies for targeting cell cycle in cancer?
ATR/ATM inhibitors, CDK2/4/6 inhibitors, Wee1 inhibitors, DNA repair inhibitors.
42
What must happen during mitosis?
Mitosis must equally segregate chromosomes to daughter cells; anaphase starts only when all are aligned.
43
How is anaphase timing regulated?
Through the Spindle Assembly Checkpoint (SAC) and Anaphase Promoting Complex (APC).
44
What role does the Mitotic Checkpoint Complex (MCC) play?
MCC sends wait signals to inhibit APC until all chromosomes are aligned.
45
How does the APC contribute to mitotic exit?
APC degrades cyclin B and securin, triggering chromosome segregation and mitotic exit.
46
What are the two key functions of the APC?
1. Degrades cyclin B to trigger mitotic exit. 2. Degrades securin to activate separase for chromosome segregation.
47
How do cells sense chromosome alignment during mitosis?
MCC senses microtubule attachments and tension at kinetochores; only correct attachments satisfy the SAC.
48
What is the effect of mutations in genes related to chromosome segregation?
Mutations disrupt mechanisms ensuring accurate chromosome segregation, leading to cancer.