Cell Division and Cycle Control

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Questions and Answers

What defines the end of the mitotic phase during cell division?

Completion of cytokinesis (correct)

Replication of DNA

The separation of sister chromatids

Formation of nuclear envelope

Which of the following is NOT a criterion for passing the G2/M checkpoint?

Large cell volume

Presence of DNA damage (correct)

Sufficient number of organelles

Complete replication of genome

Which statement about cyclins and cyclin-dependent kinases (Cdks) is accurate?

Cdk levels fluctuate while cyclin levels remain constant.

Cyclins activate Cdks by binding to them at specific stages. (correct)

Cyclin-dependent kinases remain inactive without cyclin.

Cyclin levels remain constant throughout the cell cycle.

What failure at the metaphase-to-anaphase transition checkpoint indicates a potential issue?

Chromatids not properly assembled on mitotic spindle Signup and view all the answers

Which characteristic correctly describes cyclin-dependent kinases (Cdks)?

Their activity is contingent upon cyclin binding. Signup and view all the answers

At which checkpoint does a cell verify that the genome has fully replicated without damage?

G2/M checkpoint Signup and view all the answers

What is the typical relationship between Cdk levels and cyclin levels during the cell cycle?

Cdk levels remain constant and exceed cyclin levels significantly. Signup and view all the answers

Which of the following checkpoints is responsible for determining if each kinetochore is properly attached to a spindle fiber?

Metaphase checkpoint Signup and view all the answers

What is the effect of point mutations in protein kinases like Src on enzymatic activity?

They enhance enzymatic activity and broaden substrate specificity. Signup and view all the answers

What is gene amplification in the context of cancer cells?

An increase in the number of copies of a gene, leading to excessive synthesis of its product. Signup and view all the answers

Which of the following correctly describes RAS in human tumors?

Point mutation of RAS is the most common abnormality in human tumors. Signup and view all the answers

How do GTPase-activating proteins (GAPs) affect Ras activity?

They inactivate Ras by stimulating the hydrolysis of its bound GTP. Signup and view all the answers

Which type of mutation is most frequently associated with cholangiocarcinoma and pancreatic adenocarcinoma?

Point mutation of RAS. Signup and view all the answers

What role does Myc typically play in cells experiencing gene amplification?

It is overproduced, promoting increased cell division. Signup and view all the answers

What is a common effect of errors in DNA repair or chromosome segregation?

Changes in chromosome structure leading to increased gene copy number. Signup and view all the answers

Which growth factor pathways are heavily dependent on Ras?

EGF and PDGF signal transduction pathways. Signup and view all the answers

Which phase of the cell cycle directly involves DNA synthesis?

S Phase Signup and view all the answers

What is the role of the Anaphase-Promoting Complex (APC) in the cell cycle?

To trigger sister-chromatid separation and cyclin degradation Signup and view all the answers

What is the primary role of checkpoint proteins in the cell cycle?

To enforce control mechanisms ensuring proper cell division Signup and view all the answers

Which phase of the cell cycle is primarily associated with the activation of S-Cdk complexes?

S phase Signup and view all the answers

Which tumor suppressor is associated with the G1 checkpoint and its dysfunction leading to cancer development?

RB1 Signup and view all the answers

How does genomic instability contribute to cancer progression?

By promoting the accumulation of genetic alterations Signup and view all the answers

How does a mutation in a tumor suppressor gene contribute to tumorigenesis?

By resulting in a loss of function that is usually genetically recessive Signup and view all the answers

Which of the following statements is true regarding the p53 gene?

It is known as 'THE GUARDIAN OF THE GENOME'. Signup and view all the answers

In the context of cell cycle regulation, what effect does CDK-dependent phosphorylation of Rb have?

It releases active E2F transcription factors to promote S phase entry Signup and view all the answers

What is the result of dysfunctional cell cycle checkpoints?

Increased genomic instability Signup and view all the answers

What is Knudson's two-hit hypothesis primarily concerned with?

The requirement of two mutations in tumor suppressor genes for tumor formation Signup and view all the answers

What initiates the activation of M-Cdk complexes?

Completion of DNA replication in S phase Signup and view all the answers

What event occurs during cytokinesis?

Division of the cytoplasm Signup and view all the answers

Which molecule is primarily involved in promoting cell division within the cell cycle?

Cyclin-dependent kinases (CDKs) Signup and view all the answers

What is the primary role of cyclin–Cdk complexes in the cell cycle?

To initiate transitions between different phases of the cell cycle Signup and view all the answers

What signifies the commitment of a cell to a new division cycle?

Formation of active G1/S-Cdk complexes Signup and view all the answers

What is the primary action of the Rb protein when it is hypophosphorylated?

It binds E2F transcription factors and inhibits transcription. Signup and view all the answers

Which of the following correctly describes the role of cyclin-dependent kinases (CDKs) in the G1/S transition?

CDKs phosphorylate the Rb protein, leading to E2F release. Signup and view all the answers

What consequence follows the mutation or loss of the Rb gene?

Uncontrolled cell proliferation leading to cancer. Signup and view all the answers

How does Rb protein coordinate DNA replication during the S phase?

It recruits proteins that activate S-phase gene expression. Signup and view all the answers

What inhibits the phosphorylation of the Rb protein?

Cyclin-dependent kinase inhibitors (CDKIs). Signup and view all the answers

What happens when the Rb protein is phosphorylated by CDK complexes?

It releases E2F transcription factors to activate S-phase genes. Signup and view all the answers

In what state does the Rb protein exert its anti-proliferative effects?

Hypophosphorylated and bound to E2F transcription factors. Signup and view all the answers

What role do histone deacetylases and histone methyltransferases play in relation to Rb protein?

They are recruited by Rb to inhibit transcription of certain genes. Signup and view all the answers

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.
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.