Cell Cycle

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Questions and Answers

What is the primary function of checkpoint controls in the cell cycle?

To monitor each step and ensure prerequisite completion (correct)

To facilitate energy production in cells

To increase the speed of cell division

To enhance DNA replication efficiency

What happens if a problem is detected during a specific step of the cell cycle?

The cell initiates apoptosis immediately

Progress through the cell cycle is halted (correct)

The cell replicates its DNA again

The cell continues to the next step

Which phase of the cell cycle must be completed before entering the S phase?

G2 phase

M phase

G1 phase (correct)

Telophase

What ensures that a completed step in the cell cycle is not repeated until the next cycle?

Checkpoint controls Signup and view all the answers

Which phase is monitored to halt the cell from transitioning into mitosis?

G2 phase Signup and view all the answers

What does the surveillance mechanism do during the cell cycle?

It ensures each phase proceeds without errors Signup and view all the answers

What can trigger the cell to halt its progress through the cell cycle?

Problems in specific step execution Signup and view all the answers

What is one of the requirements before a cell can enter mitosis?

Prerequisite steps must be successfully completed Signup and view all the answers

Which cyclin is responsible for directing CDK2 during the G1 phase of the cell cycle?

Cyclin E Signup and view all the answers

What is required for the catalytic function of a cyclin-dependent kinase (CDK) to become activated?

Phosphorylation by CDK-activating kinase Signup and view all the answers

During which phase of the cell cycle does cyclin A replace cyclin E?

S phase Signup and view all the answers

Which CDKs are associated with the D-type cyclins?

CDK4 and CDK6 Signup and view all the answers

What structural feature is common in all cyclin-dependent kinases (CDKs)?

PSTAIRE α-helix Signup and view all the answers

Which cyclin pairs with CDC2 during the M phase?

Cyclin B Signup and view all the answers

What is the main role of cyclin E in the cell cycle?

To prepare for the entrance into S phase Signup and view all the answers

Which CDK is involved in the transition between G1 and S phase?

CDK2 Signup and view all the answers

What role do cyclin–CDK complexes play in the cell cycle?

They regulate cell cycle progression. Signup and view all the answers

In early frog and sea urchin embryos, the levels of which cyclin fluctuate noticeably?

Cyclin B Signup and view all the answers

How do early embryos primarily progress through the cell cycle?

By alternating between M and S phases. Signup and view all the answers

What happens to cyclin B levels before the onset of M phase?

Cyclin B levels are already substantial. Signup and view all the answers

What is a notable characteristic of the cell cycles in early embryos mentioned?

All cells enter M phase simultaneously. Signup and view all the answers

What is the status of CDK3 in laboratory mice regarding cell cycle control?

It is not needed for normal cell cycle control. Signup and view all the answers

What must be modulated to impose control on specific steps in the cell cycle?

The activities of the cyclin–CDK complexes Signup and view all the answers

What is the effect of cyclin B on cell cycle progression?

It allows cyclin–CDK complexes to form. Signup and view all the answers

What is the significance of cyclins in the cell cycle?

They regulate the timing of cell cycle transitions. Signup and view all the answers

Which phase of the cell cycle requires the accumulation of B cyclins for entry?

M phase Signup and view all the answers

How do D-type cyclins respond to extracellular signals?

They only influence cell cycle progression in G1 phase. Signup and view all the answers

What ensures that cells cannot mistakenly enter an M phase after exiting it?

The slow accumulation of cyclins. Signup and view all the answers

What happens to cyclin D1 following the G1/S transition?

It is exported to the cytoplasm and no longer affects the cycle. Signup and view all the answers

Which of the following statements about mammalian cyclins is TRUE?

Their levels vary greatly as the cell progresses through different phases. Signup and view all the answers

What is the main consequence of cyclins dictating a one-way movement through the cell cycle?

Cellular processes remain orderly and prevent errors. Signup and view all the answers

Which cyclins are noted for having tightly coordinated fluctuation with the cell cycle schedule?

Most mammalian cyclins except for D-type cyclins Signup and view all the answers

What is a significant characteristic of incipient cancer cells during tumor progression?

They utilize various mutated alleles that provide a proliferative advantage. Signup and view all the answers

How does increased genome mutability affect tumor progression rates?

It accelerates the acquisition of advantageous allele combinations. Signup and view all the answers

Why are many cancer cells incompatible with normal cell cycle progression?

Their genomic instability does not activate checkpoint controls. Signup and view all the answers

What is the impact of inactivated checkpoint controls in cancer cells?

It allows cells to proceed despite DNA damage. Signup and view all the answers

Which of the following statements about embryonic stem cells (ES cells) is true?

They can generate their own signals for growth. Signup and view all the answers

What role does LIF (leukemia inhibitory factor) play in mouse ES cells?

It is required to maintain their self-renewal and prevent differentiation. Signup and view all the answers

Which statement best describes E-Ras in early mouse embryonic cells?

E-Ras is a constitutively activated protein that supports proliferation. Signup and view all the answers

What is a key difference in behavior between cells in early embryos and normal somatic cells?

Early embryonic cells follow a different set of rules for proliferation. Signup and view all the answers

What happens to TGF-β's growth-inhibitory effects after a cell passes through the R point?

It loses most of its growth-inhibitory powers. Signup and view all the answers

What is the role of p21Cip1 in response to cellular stress?

It stops a cell in its tracks by inhibiting cyclin–CDK complexes. Signup and view all the answers

How does damage to cellular DNA affect the levels of p21Cip1?

It causes rapid increases in p21Cip1 levels. Signup and view all the answers

What is the effect of p21Cip1 on cyclin–CDK complexes?

It shuts down their activity in response to DNA damage. Signup and view all the answers

What happens when genomic DNA is damaged during the G1 phase?

p21Cip1 prevents the cell from advancing through the R point. Signup and view all the answers

What effect does TGF-β have on p15INK4B mRNA synthesis in keratinocytes?

It induces a dramatic increase in p15INK4B synthesis. Signup and view all the answers

Why is p21Cip1 particularly important during the G1 phase of the cell cycle?

It blocks the cell from advancing until damage is repaired. Signup and view all the answers

In what way does p21Cip1 affect already-formed cyclin–CDK complexes after DNA damage?

It prevents their activity until repair is complete. Signup and view all the answers

Study Notes

pRb and Control of the Cell Cycle Clock

Cell fate is dictated by signals from surroundings
Most cells won't proliferate without mitogenic growth factors
TGF-β can override mitogenic factors, halting proliferation
Extracellular signals are received by cell surface receptors, processed, integrated, and distilled to simple binary decisions about proliferation or quiescence
A master governor - the cell cycle clock, residing in the nucleus, directs these decisions
The cell cycle clock is a network of interacting proteins acting as a signal-processing circuit.
Cancer cells are influenced by normal and oncogene proteins that disrupt normal control
Oncogenes and tumor suppressor genes disrupt cell cycle clock circuitry
Cell growth and division is coordinated by regulators.
Cells formed by division must decide whether to grow or go into quiescence, which can be reversible or irreversible.
Cell growth precedes cell division through the accumulation of cellular constituents to ensure two daughter cells receive a complete endowment
DNA duplication occurs immediately after cell division in some prokaryotic cells, but is deferred in many mammalian cells
Cell cycle clock dictates proliferation or quiescence
Master governor (cell cycle clock) receives various incoming signals
Cells can be post-mitotic and not able to proliferate further
Decisions are made in G1 phase.
Extracellular signals govern actions through the restriction point (R point.)
Post-R point decision unaffected by lack of growth factors
Tumor progression frequently involves mutations that cause uncontrolled proliferation rate.
Disturbance in checkpoint controls contributes to unregulated cell proliferation.
DNA damage or other errors can halt cell cycle progression until repaired.
Checkpoints block advance through the cell cycle until preceding conditions are met.
Checkpoints ensure a particular step is not repeated until the next cell cycle.

Cyclins and Cyclin-dependent kinases

These proteins are the core components of the cell cycle clock.
Cyclins activate CDKs to execute cell cycle processes.
CDKs are serine/threonine kinases
Cyclins are regulatory subunits needed by CDKs.
Various cyclin-CDK combinations carry out tasks, like phosphorylation of proteins.
Cyclin levels fluctuate throughout the cell cycle
For example, cyclin B levels are high during the M phase and very low subsequently, allowing the cell to enter M-phase smoothly.
Different Cyclins target CDKs to specific processes of the cell cycle.
D cyclins partner with CDK4/6
E cyclins partner with CDK2
A cyclins partner with CDK2 or CDC2
B cyclins partner with CDC2.
Precise timing is crucial

Checkpoint Controls

Cell cycle progression is monitored by checkpoints regulating each step.
Cell is prevented from advancing to next step if prior steps are not completed.
Errors in cell cycle phases are actively prevented.
Critical timing is crucial for proper cell function.
Checkpoints regulate cell cycle transitions and ensure fidelity.

pRb function

pRb acts as a guardian of the cell's restriction point functioning through phosphorylation
Initially, pRb is inactive in G₀, becoming slightly phosphorylated in G₁ and becoming entirely hyperphosphorylated when the cell passes through the restriction point which in turn triggers the activation of E2F.
P-Rb is actively growth-inhibitory in G₁, inactive when hyperphosphorylated
Viral oncoproteins (E1A from adenovirus, Large T from SV40, and E7 from human papillomavirus) target and disable pRb, leading to cancerous proliferation
Loss of pRb or inability to fully phosphorylate pRb (due to gene inactivation or mutation) is frequently associated with several cancers.
pRb regulates cell-cycle progression and differentiation through interactions with E2F transcription factors.
The phosphorylation state of pRb is essential for controlling cell proliferation and differentiation.
Different levels of pRb activation determine if the cell passes through the R point.

TGF-β and Myc

TGF-β is essential for cell growth inhibition and controlling proliferation in normal cells.
TGF-β regulates cyclin production in a way that can oppose downstream effects of myc activation.
Myc is a transcription factor promoting proliferation by regulating downstream targets.
Myc is frequently overexpressed in several cancers.
Myc can override cell cycle control resulting in unregulated proliferation.
Myc and TGF-β antagonize one another, indicating cross-regulation.
TGF-β blocks Rb phosphorylation and blocks cell cycle, while Myc drives Rb inactivation and promotes it.
These interactions emphasize the delicate balance between growth and other essential cellular processes

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