Cell Cycle and Tissue Homeostasis

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Questions and Answers

Which of the following scenarios would most likely result in a cell undergoing apoptosis due to the activity of the G2-M checkpoint?

  • A cell experiences a complete failure of DNA replication, leading to extensive DNA damage. (correct)
  • A cell with a minor DNA replication error is exposed to a broad spectrum CKI medication.
  • A cell successfully repairs a minor DNA error detected during the S phase.
  • A cell experiences normal cyclin and CDK activity throughout the G2 phase.

How would the introduction of a drug that inhibits p53 affect cells with significant DNA damage?

  • It would cause cells to undergo immediate and rapid apoptosis.
  • It would cause cells to enter a state of permanent quiescence, like a neuron.
  • It would enhance the DNA repair mechanisms, allowing the cell to recover.
  • It would allow cells with damaged DNA to bypass checkpoints and continue dividing. (correct)

In a rapidly dividing cancer cell, what would be the most likely effect of a mutation that disables the cell's ability to degrade cyclins?

  • The cell cycle would progress uncontrollably, bypassing normal regulatory checkpoints. (correct)
  • The cell cycle would slow down, providing more time for DNA repair.
  • The cell would undergo apoptosis due to the accumulation of cyclins.
  • The cell cycle would pause indefinitely at all checkpoints, preventing further division.

A researcher discovers a novel protein that, when active, prevents the binding of cyclin-CDK complexes to their target proteins. Which phase of the cell cycle would this protein most likely disrupt?

<p>It would prevent the G1-S phase transition. (C)</p> Signup and view all the answers

A new drug is designed to specifically target and inhibit CDK4 and CDK6. What is the most likely intended outcome of this drug in cancer treatment?

<p>To prevent phosphorylation of Rb protein, halting the cell cycle in G1. (B)</p> Signup and view all the answers

Why are tissues with high cell turnover rates, such as the gastrointestinal tract and epidermis, more susceptible to cancer development?

<p>Because their high rate of cell division increases the likelihood of DNA replication errors. (D)</p> Signup and view all the answers

How do cancer cells typically overcome the normal cell cycle checkpoints, allowing them to proliferate uncontrollably?

<p>By developing mutations that disable or bypass checkpoint controls. (A)</p> Signup and view all the answers

A mutation inactivates the gene for p21, a CKI. How would this mutation affect the cell cycle in normal, healthy cells?

<p>It would allow the cell cycle to proceed more quickly, even in the presence of DNA damage. (B)</p> Signup and view all the answers

In a tissue sample from a patient with an aggressive form of cancer, researchers observe unusually high levels of Cyclin D. What is the most likely implication of this finding?

<p>The cells are rapidly progressing through G1-S restriction point. (B)</p> Signup and view all the answers

Why is the development of drugs that target cell cycle checkpoints a promising but challenging approach in cancer therapy?

<p>Because cancer cells can develop resistance to these drugs through various adaptive mechanisms. (C)</p> Signup and view all the answers

Flashcards

Cell Cycle

Succession of events happening in a specific order to assure cell proliferation.

G0 Phase

Cells that are not actively cycling; quiescent cells.

Permanent Cells

Permanent cells that have lost the capacity to proliferate and are forever in G0.

Labile Cells

Cells with a high cell turnover that cycle continuously, such as cells of gastrointestinal tract and epidermis.

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Checkpoints (G1-S, G2-M)

Act as filters, stopping aberrant cells from progressing in the cell cycle.

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Cyclins

Proteins that bind with cyclin-dependent kinases (CDK) to form complexes that drive the cell cycle.

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Cyclin-Dependent Kinases (CDKs)

Enzymes that, when bound to cyclins, phosphorylate substrates, promoting cell cycle progression.

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G1-S Checkpoint

Ensures DNA integrity before allocating resources for DNA replication.

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G2-M Checkpoint

Ensures that DNA replication was completed accurately before mitosis begins.

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Cyclin-Dependent Kinase Inhibitors (CKIs)

Proteins that act on cyclin-CDK complexes to halt cell cycle progression.

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Study Notes

  • The cell cycle is a series of events that leads to cell proliferation
  • It is fundamental for organism development and maintaining tissue homeostasis.
  • Tissue homeostasis replaces dead or damaged cells.
  • Stem cells are important in tissue homeostasis because of their regenerative capabilities.
  • Accurate DNA replication is crucial for cell division.

Cell Cycle Phases

  • G0 (Quiescence): Cells are not actively cycling
  • G1 (Gap 1): Cell grows and prepares for DNA synthesis.
  • S (Synthesis): DNA is replicated.
  • G2 (Gap 2): Cell prepares for mitosis.
  • M (Mitosis): Cell divides into two daughter cells.
  • Neurons and cardiac myocytes are permanent cells in G0 that cannot proliferate
  • Hepatocytes are stable cells in G0 that can re-enter the cell cycle.
  • Gastrointestinal and skin cells are labile tissues with high turnover rates and frequent division.

Cell Cycle Checkpoints

  • G1-S checkpoint monitors DNA integrity before DNA replication starts
  • G2-M checkpoint confirms DNA replication completed accurately before mitosis.
  • Checkpoints prevent cells with damaged or unduplicated DNA from progressing through the cell cycle.
  • Cancer cells evade checkpoints, leading to uncontrolled proliferation.

Regulation of Cell Cycle

  • Activators and inhibitors regulate the cell cycle.
  • Cyclins bind to cyclin-dependent kinases (CDKs), forming cyclin-CDK complexes.
  • Cyclin-CDK complexes phosphorylate substrates and promote cell cycle progression.
  • Cyclins A, B, D, and E are the most important.
  • Cyclin synthesis increases during cell cycle stages, activating CDK complexes.
  • After cell cycle completion, cyclins degrade, and CDK activity decreases.

G1 to S Phase Transition

  • At the G1-S transition, the G1 restriction point ensures DNA integrity.
  • Retinoblastoma protein (Rb) phosphorylation is regulated by Cyclin D-CDK4/6 and Cyclin A-CDK2 complexes.

S Phase to G2-M Transition

  • During the S phase DNA is replicated
  • The G2-M restriction point confirms DNA replication is complete before mitosis.
  • Cyclin B-CDK1 complexes regulate the G2-M checkpoint.
  • DNA defects trigger DNA repair mechanisms or division delay.
  • Severe DNA damage induces senescence (permanent growth arrest) or apoptosis (programmed cell death).

Inhibitors of Cell Cycle

  • Cyclin-dependent kinase inhibitors (CKIs) act on cyclin-CDK complexes.
  • Broad-spectrum inhibitors include p21, p27, and p57.
  • Specific inhibitors include p15, p16, p18, and p19, which act on CDK4 and CDK6.
  • Understanding molecular mechanisms of the cell cycle is crucial for developing cancer therapies.

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