[MODULE 2] Checkpoints

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35 Terms

1
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What are the characteristics of cell cycle switches?

  • binary (complete, irreversible)

  • remarkably robust

  • highly adaptable to different cell types and signals

2
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What are the three major regulatory transitions in the cell cycle?

  • Start/restriction point

  • G2/M Transition

  • Metaphase to Anaphase Transition

3
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_________ the first checkpoint in G1, where the cell commits to DNA replication. Removing signals after this point does not stop the cell cycle.

Start/Restriction point

4
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Checkpoint that checks whether all DNA is replicated and the environment is favorable for division. If not, it can enter G0 or undergo apoptosis.

G2/M Transition checkpoint

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Ensures proper chromosomal alignment and checks for chromosomal abnormalities before separation of sister chromatids.

Metaphase-to-Anaphase Transition

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What types of cells undergo mitosis without cytokinesis, resulting in multinucleated cells?
______ - responsible for platelet production, skeletal muscles, liver cells, and some plant cells.

Megakaryocytes

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Processes included in the M phase

Nuclear division (mitosis) and cytoplasmic division (cytokinesis)

8
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How much time is typically spent in interphase during the cell cycle?


22-23 hours

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What are the three phases of interphase?


G1 phase

S phase

G2 phase

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What types of errors does the G2 phase check for?


Unreplicated or damaged DNA.

11
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It is an artificial thymidine analog incorporated into newly synthesized DNA in S-phase cells.

5-ethynyl-2'-deoxyuridine (EdU)

12
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How do cyclin levels change during the cell cycle?



  • Changes in protein levels result in cyclic assembly and activation of cyclin-Cdk complexes.

  • G1 cyclins respond to extracellular signals and govern G1/S-cyclins activity.

13
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What are the central components of the cell-cycle control system?


  • Cyclin-dependent protein kinases (Cdks)

  • Cyclin subunits

  • APC/C and SCF ubiquitin ligases

  • Oscillations in cyclin-Cdk complex activities control cell-cycle events.

14
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pace the cell cycle by phosphorylating intracellular proteins, initiating major cell-cycle events

Cyclin-Dependent Protein Kinases (Cdks)

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What activates Cdks to move forward with cell cycle by adding an additional phosphate group

Cdk-activating kinase (CAK)

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adds inhibitory phosphorylation to Cdks, preventing their activity before mitosis (G2/M); prevents cells with DNA damage from entering mitosis prematurely

Wee1 kinase

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removes inhibitory phosphates from Cdks, activating them at the onset of mitosis

Cdc25 phosphatase

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inactivates cyclin-Cdk complex , inhibiting progression through the G1/S checkpoint.

CKIs (Cdk Inhibitor Proteins), ex: p27

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TRUE OR FALSE:
Cdk is always present in cells but activation varies depending on amount of Cyclin

TRUE

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It enhances the progression through the cell cycle by amplifying the signals that move the cell to the next stage; moves away from homeostasis

Positive feedback

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Examples of positive feedback regulators

CDK4,6 + Cyclin D1,2,3

CDK2 + Cyclin E

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Inhibit progression and moves toward homeostasis

Negative feedback

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Examples of negative feedback regulators

INK4 (p15,16,18,19)

KIP/CIP (P21,27,57)

Cyclin G2

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_______ - reverses the effects of Cdks by dephosphorylation, acting as an anti-cell division mechanism

Protein Phosphatase 2A (PP2A)

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How does M-Cdk activate during mitosis?

M-Cdk activation involves positive feedback, where phosphorylated M-Cdk stimulates Cdc25 and inhibits Wee1, enhancing mitotic progression

26
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_____ tags proteins (e.g., S or M cyclins) for degradation in proteasomes, leading to Cdk inactivation.

Ubiquitin

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initiates the transition from metaphase to anaphase by degrading proteins like securin, leading to chromatid separation.

Anaphase-Promoting Complex (APC/C)

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  • Activated by Cdc20 and Cdh1 to transition from metaphase to anapase

  • induces the disassociation of cohesin complex

Anaphase-promoting complex/cyclosome (APC/C)

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triggers initial ativation of APC/C at metaphase to anaphase; stimulated by M-Cdk activity

Cdc20

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Maintains APC/C activity after anaphase and throughout G1, inhibited by Cdk activity

Cdh1

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POSITIVE OR NEGATIVE FEEDBACK
APC/C-Cdc20 turns itself off by inactivating Cdks, leading to APC/C dephosphorylation and inactivation in anaphase

Negative

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  • Involved in the destruction of G1/S-cyclins and CKIs, promoting the transition from G1 to S phase and facilitating DNA replication.

  • Protein complex for ubiquitination

SKP, CULLIN, F-BOX (SCF)

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cyclin (Cyclin A) bound to Cdk2, initiates DNA replication once per cycle

S-Cdk Complex

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  • Shorten every division

  • Gives signal to cell that it is old

  • Old cells more likely to have mutations (e.g. cancer in old people)

Telomeres

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What prevents endless cell division in normal cells?

Hayflick limit