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Questions and Answers
What defines the end of the mitotic phase during cell division?
Which of the following is NOT a criterion for passing the G2/M checkpoint?
Which statement about cyclins and cyclin-dependent kinases (Cdks) is accurate?
What failure at the metaphase-to-anaphase transition checkpoint indicates a potential issue?
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Which characteristic correctly describes cyclin-dependent kinases (Cdks)?
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At which checkpoint does a cell verify that the genome has fully replicated without damage?
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What is the typical relationship between Cdk levels and cyclin levels during the cell cycle?
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Which of the following checkpoints is responsible for determining if each kinetochore is properly attached to a spindle fiber?
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What is the effect of point mutations in protein kinases like Src on enzymatic activity?
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What is gene amplification in the context of cancer cells?
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Which of the following correctly describes RAS in human tumors?
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How do GTPase-activating proteins (GAPs) affect Ras activity?
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Which type of mutation is most frequently associated with cholangiocarcinoma and pancreatic adenocarcinoma?
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What role does Myc typically play in cells experiencing gene amplification?
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What is a common effect of errors in DNA repair or chromosome segregation?
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Which growth factor pathways are heavily dependent on Ras?
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Which phase of the cell cycle directly involves DNA synthesis?
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What is the role of the Anaphase-Promoting Complex (APC) in the cell cycle?
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What is the primary role of checkpoint proteins in the cell cycle?
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Which phase of the cell cycle is primarily associated with the activation of S-Cdk complexes?
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Which tumor suppressor is associated with the G1 checkpoint and its dysfunction leading to cancer development?
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How does genomic instability contribute to cancer progression?
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How does a mutation in a tumor suppressor gene contribute to tumorigenesis?
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Which of the following statements is true regarding the p53 gene?
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In the context of cell cycle regulation, what effect does CDK-dependent phosphorylation of Rb have?
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What is the result of dysfunctional cell cycle checkpoints?
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What is Knudson's two-hit hypothesis primarily concerned with?
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What initiates the activation of M-Cdk complexes?
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What event occurs during cytokinesis?
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Which molecule is primarily involved in promoting cell division within the cell cycle?
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What is the primary role of cyclin–Cdk complexes in the cell cycle?
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What signifies the commitment of a cell to a new division cycle?
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What is the primary action of the Rb protein when it is hypophosphorylated?
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Which of the following correctly describes the role of cyclin-dependent kinases (CDKs) in the G1/S transition?
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What consequence follows the mutation or loss of the Rb gene?
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How does Rb protein coordinate DNA replication during the S phase?
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What inhibits the phosphorylation of the Rb protein?
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What happens when the Rb protein is phosphorylated by CDK complexes?
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In what state does the Rb protein exert its anti-proliferative effects?
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What role do histone deacetylases and histone methyltransferases play in relation to Rb protein?
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Study Notes
Cytokinesis
- The final stage of mitosis where two daughter cells separate.
- Each daughter cell contains a nucleus and cytoplasmic organelles.
Cell Cycle Checkpoints
-
Start checkpoint (G1/S)
- Checks for sufficient organelles and cell volume.
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G2/M checkpoint
- Checks for a fully replicated genome and large cell volume.
-
Metaphase-to-anaphase transition
- Checks for attachment of each kinetochore to a spindle fiber and ensures chromatids are properly assembled on the mitotic spindle.
- Failure of any checkpoint can lead to DNA damage and cell cycle arrest.
Cyclin-Dependent Kinase Activation
- The cell cycle control system relies on cyclin-dependent kinases (Cdks).
- Cdks are activated at specific cell cycle stages by regulatory subunits called cyclins.
- Cyclins fluctuate in levels throughout the cell cycle.
- Cdks are crucial for the cell cycle control system.
Oscillations in Cyclin Levels
- Levels of three major cyclin types oscillate throughout the cell cycle.
- This drives oscillations in cyclin-Cdk complexes responsible for cell cycle events.
- Cdk levels remain constant and exceed cyclin levels.
- Cyclin-Cdk complexes form parallel to cyclin levels.
Phases of the Cell Cycle
- G1/S-Cdk complexes: commit the cell to a new division cycle at the Start checkpoint in late G1.
- S-Cdk complexes: initiate DNA replication at the beginning of S phase.
- M-Cdk activation: occurs after the completion of S phase, leading to progression through the G2/M checkpoint and mitotic spindle assembly.
Anaphase-Promoting Complex (APC) Activity
- Triggers sister-chromatid separation during the metaphase-to-anaphase transition.
- Inactivates Cdks by degrading S and M cyclins.
- Promotes completion of mitosis and cytokinesis.
- Maintained in G1 until G1/S-Cdk activity rises again.
Tumor Suppressor Genes
- Encode proteins that normally restrain cell proliferation and tumorigenesis.
- Mutations in these genes increase the likelihood of cancer formation.
- Loss of function is often recessive, requiring mutations in both copies of the gene.
- Regulate cell growth by inhibiting proliferation.
- Their loss of function is a key event in carcinogenesis.
Knudson's Two-Hit Hypothesis
- Proposed by Alfred Knudson in 1971.
- Based on epidemiological studies of retinoblastoma.
- Explains the genetic basis of retinoblastoma, a tumor of the retina that can be inherited or occur sporadically.
Rb Protein Role in Cell Cycle
- G1/S Transition: When appropriate signals for proliferation are received (like growth factors), CDKs are activated.
- Phosphorylation of Rb: CDKs phosphorylate Rb, releasing E2F transcription factors.
- E2F Activation: Released E2F proteins activate genes required for DNA replication and entry into the S phase of the cell cycle.
Rb Protein in DNA Replication
- Continues to play a role in coordinating DNA replication during S phase.
- Ensures accurate replication and controlled cell cycle progression.
Rb Protein Function
- Acts as a tumor suppressor by regulating cell cycle progression and preventing uncontrolled cell division.
- Mutations or loss of the Rb gene can lead to cancer.
RB Protein and Transcription Factors
- Hypophosphorylated Rb binds to E2F transcription factors and inhibits transcription of S phase genes.
- Phosphorylation of Rb by CDK4, CDK6, and CDK2 complexes releases E2F.
- E2F activates transcription of S-phase genes.
- CDKIs inhibit the phosphorylation of Rb by inactivating cyclin-CDK complexes.
Rb Protein and Cell Cycle Control
- Plays a critical role in regulating the cell cycle by controlling the G1-to-S phase transition.
- In its active form, Rb is hypophosphorylated and binds to E2F, inhibiting cell proliferation.
- Mutations in RB can lead to excessive cell proliferation and cancer.
Mechanisms of Oncogene Activation
- Point Mutations: Occur in specific genes, altering the function of their encoded proteins.
- Gene Amplification: Increase in the number of copies of a gene, leading to overproduction of the gene product.
- Translocation or Transposition: Changes in chromosome structure or number that can increase gene copy number.
RAS Gene
- Most commonly mutated oncogene in human tumors.
- Point mutation of RAS is the most frequent abnormality in human tumors.
- Multiple growth factor signal transduction pathways depend on RAS.
- Mutated in 15-20% of cancers.
RAS Function and Regulation
- Small GTPase that acts as a molecular switch.
- Active when bound to GTP and inactive when bound to GDP.
- GTPase-activating proteins (GAPs) inactivate Ras by stimulating GTP hydrolysis.
- Guanine nucleotide exchange factors (GEFs) activate Ras by promoting GTP binding.
Cell Cycle and Cancer
- Dysregulation of the cell cycle is a fundamental feature of cancer development.
- Uncontrolled cell growth and division are hallmarks of cancer.
- Cell cycle control mechanisms are disrupted in cancer.
Disrupted Cell Cycle Checkpoints
- Cell cycle checkpoints are essential for ensuring proper cell cycle progression.
- Loss or dysfunction of these checkpoints can lead to genetic instability and contribute to cancer development.
- Defects in the G1 checkpoint can allow cells with DNA damage to enter the cell cycle.
Genomic Instability
- Dysregulation of the cell cycle can lead to genomic instability, a hallmark of cancer.
- Errors in DNA replication, impaired DNA repair, and chromosome missegregation contribute to genomic instability.
- This fuels the genetic diversity of cancer cells, promoting tumor progression.
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Description
This quiz covers key concepts in cytokinesis and cell cycle checkpoints, including the critical roles of cyclin-dependent kinases and the regulation of cyclin levels. Test your understanding of how these processes ensure proper cell division and the consequences of failures in the cell cycle control system.