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?

<p>Checkpoint controls (B)</p> Signup and view all the answers

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

<p>G2 phase (D)</p> Signup and view all the answers

What does the surveillance mechanism do during the cell cycle?

<p>It ensures each phase proceeds without errors (D)</p> Signup and view all the answers

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

<p>Problems in specific step execution (B)</p> Signup and view all the answers

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

<p>Prerequisite steps must be successfully completed (D)</p> Signup and view all the answers

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

<p>Cyclin E (D)</p> Signup and view all the answers

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

<p>Phosphorylation by CDK-activating kinase (A)</p> Signup and view all the answers

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

<p>S phase (C)</p> Signup and view all the answers

Which CDKs are associated with the D-type cyclins?

<p>CDK4 and CDK6 (C)</p> Signup and view all the answers

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

<p>PSTAIRE α-helix (C)</p> Signup and view all the answers

Which cyclin pairs with CDC2 during the M phase?

<p>Cyclin B (B)</p> Signup and view all the answers

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

<p>To prepare for the entrance into S phase (C)</p> Signup and view all the answers

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

<p>CDK2 (B)</p> Signup and view all the answers

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

<p>They regulate cell cycle progression. (C)</p> Signup and view all the answers

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

<p>Cyclin B (C)</p> Signup and view all the answers

How do early embryos primarily progress through the cell cycle?

<p>By alternating between M and S phases. (C)</p> Signup and view all the answers

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

<p>Cyclin B levels are already substantial. (B)</p> Signup and view all the answers

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

<p>All cells enter M phase simultaneously. (B)</p> Signup and view all the answers

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

<p>It is not needed for normal cell cycle control. (A)</p> Signup and view all the answers

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

<p>The activities of the cyclin–CDK complexes (D)</p> Signup and view all the answers

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

<p>It allows cyclin–CDK complexes to form. (B)</p> Signup and view all the answers

What is the significance of cyclins in the cell cycle?

<p>They regulate the timing of cell cycle transitions. (A)</p> Signup and view all the answers

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

<p>M phase (A)</p> Signup and view all the answers

How do D-type cyclins respond to extracellular signals?

<p>They only influence cell cycle progression in G1 phase. (C)</p> Signup and view all the answers

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

<p>The slow accumulation of cyclins. (D)</p> Signup and view all the answers

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

<p>It is exported to the cytoplasm and no longer affects the cycle. (C)</p> Signup and view all the answers

Which of the following statements about mammalian cyclins is TRUE?

<p>Their levels vary greatly as the cell progresses through different phases. (B)</p> Signup and view all the answers

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

<p>Cellular processes remain orderly and prevent errors. (A)</p> Signup and view all the answers

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

<p>Most mammalian cyclins except for D-type cyclins (D)</p> Signup and view all the answers

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

<p>They utilize various mutated alleles that provide a proliferative advantage. (C)</p> Signup and view all the answers

How does increased genome mutability affect tumor progression rates?

<p>It accelerates the acquisition of advantageous allele combinations. (A)</p> Signup and view all the answers

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

<p>Their genomic instability does not activate checkpoint controls. (C)</p> Signup and view all the answers

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

<p>It allows cells to proceed despite DNA damage. (A)</p> Signup and view all the answers

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

<p>They can generate their own signals for growth. (D)</p> Signup and view all the answers

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

<p>It is required to maintain their self-renewal and prevent differentiation. (A)</p> Signup and view all the answers

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

<p>E-Ras is a constitutively activated protein that supports proliferation. (C)</p> Signup and view all the answers

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

<p>Early embryonic cells follow a different set of rules for proliferation. (C)</p> Signup and view all the answers

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

<p>It loses most of its growth-inhibitory powers. (C)</p> Signup and view all the answers

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

<p>It stops a cell in its tracks by inhibiting cyclin–CDK complexes. (D)</p> Signup and view all the answers

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

<p>It causes rapid increases in p21Cip1 levels. (D)</p> Signup and view all the answers

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

<p>It shuts down their activity in response to DNA damage. (C)</p> Signup and view all the answers

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

<p>p21Cip1 prevents the cell from advancing through the R point. (B)</p> Signup and view all the answers

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

<p>It induces a dramatic increase in p15INK4B synthesis. (D)</p> Signup and view all the answers

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

<p>It blocks the cell from advancing until damage is repaired. (C)</p> Signup and view all the answers

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

<p>It prevents their activity until repair is complete. (D)</p> Signup and view all the answers

Flashcards

Cell Cycle Checkpoints

Mechanisms that monitor each step of the cell cycle and allow progression only if prerequisites are met; they halt if a step goes wrong.

Cell Cycle Progression

The ordered series of events in a cell that leads to cell division.

Checkpoint Control

Another name for cell cycle checkpoints.

Cell Cycle Surveillance

The cell's monitoring system for cell cycle progression.

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DNA Replication

The process of copying the cell's DNA before cell division.

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Mitotic Spindle

Structure involved in chromosome separation during mitosis.

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G2 Phase

A stage in the cell cycle where cell growth and preparation for division occur before mitosis.

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S Phase

Stage in the cell cycle where DNA replication takes place.

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Tumor Progression

The process by which cancer cells develop and spread, driven by mutations and genetic instability.

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Genomic Instability

Frequent changes in the DNA of a cell, common in cancer cells disrupting normal processes.

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Cell Cycle Checkpoints

Control mechanisms in the cell cycle that prevent progression if DNA is damaged.

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Oncogenes

Genes that promote cell growth and division, when mutated, they can accelerate cancer cell development.

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Tumor Suppressor Genes

Genes that normally prevent the development of cancer by controlling cell growth.

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Increased Mutability

Higher rate of mutations in a cell's DNA, which accelerates cancer development.

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Inactivated Checkpoints

Cancer cells often have dysfunctional cell cycle checkpoints, allowing uncontrolled growth.

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Embryonic Stem Cells

Cells from early embryos with high autonomy (self-driving characteristics) and self-proliferation mechanisms.

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Cyclin E

A cyclin that directs CDK2 to substrate proteins for phosphorylation during the G1 phase, facilitating cell cycle progression into S phase.

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CDK2

A cyclin-dependent kinase that, when paired with cyclins, directs phosphorylation of proteins crucial for cell cycle phases.

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Phosphorylation

The process of attaching phosphate groups to proteins, often activating or deactivating them.

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S Phase

The cell cycle phase in which DNA replication occurs.

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Cyclin A

A cyclin that replaces cyclin E during S phase to direct CDK2, ensuring DNA replication proceeds.

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Cyclin-Dependent Kinase (CDK)

An enzyme that phosphorylates proteins and is activated by cyclins to regulate the cell cycle.

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G1 Phase

The cell cycle phase where cells prepare for DNA replication, including growth and other essential processes before entering the S Phase.

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Cyclins

Proteins that activate CDKs, regulating various stages of the cell cycle.

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Cyclin-CDK complexes

Protein complexes that regulate cell cycle progression

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Cell cycle progression

Orderly series of events leading to cell division

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Cyclin B levels

Fluctuate during cell cycle, peaking at M phase

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S and M Phases

Key phases in the cell cycle including DNA replication and mitosis

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CDK3 and Cell Cycle Control

Laboratory mice lacking CDK3 suggest it's dispensable for typical cell-cycle control

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Modulation of Cyclin-CDK activity

Regulation of specific cell cycle steps by controlling Cyclin-CDK

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Frog and Sea Urchin Embryos

Early stage embryos with synchronous cell cycles that show cyclin fluctuations

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G1/G2 phases in early embryos

Short or absent in early embryos, cycling is mainly between M and S phase

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Cyclin levels in cell cycle

Cyclin levels rise and fall during the cell cycle, driving cell cycle progression in one direction.

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Cyclin B

Cyclin associated with the M phase of cell cycle

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D-type cyclins

Levels of D-type cyclins are influenced by external signals, specifically, growth factors.

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Cyclin E

Cyclin that leads to S phase entry through activation of CDK2

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Cyclin A

Cyclin involved in S phase DNA replication.

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Cell cycle directionality

The cell cycle progresses in one direction, preventing accidental backward steps.

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Exported cyclin D1

After G1/S transition, cyclin D1 moves from nucleus to cytoplasm, losing its cell cycle influence.

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Cell cycle phases (G1/S/G2/M)

Cell cycle has distinct phases (G1, S, G2, and M), orchestrated by specific cyclin levels.

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p21Cip1's role in response to cellular DNA damage

p21Cip1 is induced by DNA damage, halting the cyclin-CDK complexes and preventing cell cycle progression until repair occurs.

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TGF-β's effect on p15INK4B mRNA

TGF-β dramatically increases the production of p15INK4B mRNA, a cell cycle regulator.

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Cyclin-CDK complexes & G1 phase

Cyclin-CDK complexes, like E-CDK2, are active throughout the cell cycle. TGF-β's effects on growth inhibition happen early on in G1.

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p21Cip1's impact on cell cycle

p21Cip1, a CDK inhibitor, can shut down cyclin–CDK complexes after the R point in late G1. Damage-induced levels halt the cycle.

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TGF-β's effect on cell growth

TGF-β is a growth inhibitor during early and mid-G1, losing its inhibitory power later in the cell cycle.

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Cyclin-CDK complexes and the R point

After passing the R point, cyclin-CDK complexes become less controlled by growth inhibitors. p21Cip1 can block them from acting.

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R point in Cell Cycle

The R point occurs in late G1 and is a crucial cell cycle checkpoint indicating whether a cell will enter S phase or not.

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DNA damage and cell cycle arrest

Damage to DNA triggers the increase of p21Cip1, causing cell cycle arrest to allow for repair.

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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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