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Questions and Answers
What is the primary function of the G1 checkpoint in the cell cycle?
What is the primary function of the G1 checkpoint in the cell cycle?
The M checkpoint occurs after the S phase.
The M checkpoint occurs after the S phase.
False
What are two mechanisms that control the transition from the G2 phase to the M phase?
What are two mechanisms that control the transition from the G2 phase to the M phase?
G2 checkpoint and CDK activation
The __________ transcription factor is involved in the regulation of the G1 phase of the cell cycle.
The __________ transcription factor is involved in the regulation of the G1 phase of the cell cycle.
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Match the checkpoint with its corresponding phase transition:
Match the checkpoint with its corresponding phase transition:
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Which checkpoint ensures that all chromosomes are properly aligned before proceeding with mitosis?
Which checkpoint ensures that all chromosomes are properly aligned before proceeding with mitosis?
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The G2 checkpoint only assesses DNA integrity.
The G2 checkpoint only assesses DNA integrity.
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What is the role of Rb in cell cycle regulation?
What is the role of Rb in cell cycle regulation?
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Which cyclins are associated with the G1 phase?
Which cyclins are associated with the G1 phase?
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The activation of MPF leads to the inactivation of APC during the G2/M transition.
The activation of MPF leads to the inactivation of APC during the G2/M transition.
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What happens to Rb in the late G1 phase?
What happens to Rb in the late G1 phase?
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APC remains active during _______ phases.
APC remains active during _______ phases.
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Match the cell cycle components with their functions:
Match the cell cycle components with their functions:
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Which cyclin-cdk complex is involved in the S phase?
Which cyclin-cdk complex is involved in the S phase?
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P53 is responsible for promoting the cell cycle when DNA damage is detected.
P53 is responsible for promoting the cell cycle when DNA damage is detected.
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What role does E2F play in the cell cycle?
What role does E2F play in the cell cycle?
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Which of the following is responsible for phosphorylating Rb to inactivate it during the G1 phase?
Which of the following is responsible for phosphorylating Rb to inactivate it during the G1 phase?
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E2F directly promotes the transcription of genes required for the G1 phase.
E2F directly promotes the transcription of genes required for the G1 phase.
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What happens to the cell if the mitogen is removed?
What happens to the cell if the mitogen is removed?
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The cyclin that complexes with cdk-2 for synthesis in the S phase is called __________.
The cyclin that complexes with cdk-2 for synthesis in the S phase is called __________.
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Match each cyclin-cdk complex with its associated phase:
Match each cyclin-cdk complex with its associated phase:
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Which transcription factors are mentioned as early response genes?
Which transcription factors are mentioned as early response genes?
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Cyclin-E/CDK2 is responsible for the initiation of DNA replication.
Cyclin-E/CDK2 is responsible for the initiation of DNA replication.
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What is the role of Rb in the cell cycle?
What is the role of Rb in the cell cycle?
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Study Notes
Cell Cycle Regulation
- The cell cycle is a series of events that take place in a cell leading to its duplication.
- The cell cycle is tightly controlled by tumour suppressor genes to prevent uncontrolled cell growth.
- The protein products of tumour suppressor genes inhibit cell division.
- Two important tumour suppressor genes are RB1 and TP53.
- These two produce proteins Rb and p53 respectively.
- Cell cycle control is maintained by protein complexes composed of two subunits: cyclin (cyc) and cyclin-dependent kinase (cdk).
- Kinases are enzymes that inactivate/activate other proteins by phosphorylation.
- The concentration of cyclins fluctuates in the cell.
- The active form of cdks (cyc-cdk) can phosphorylate various proteins, leading to protein activation or inactivation, e.g. phosphorylation of G1/S transcription factors.
- The activity of cdks is regulated by degradation of cyclins by the proteasome.
- The proteasome is a giant protein complex that degrades short-lived proteins, such as cyclins and misfolded proteins.
- Proteins destined for degradation are first tagged with ubiquitin, a small regulatory protein.
- Addition of ubiquitin is facilitated by enzymes called ubiquitin ligases (E3 ligases).
Phases of the Cell Cycle
- The cell cycle consists of interphase and the mitotic phase.
- Interphase includes G1, S, and G2 phases.
- The mitotic phase (M) includes mitosis and cytokinesis.
- The figure 12.5 shows the schematic representation of the cell cycle.
Cell Cycle Checkpoints
- Checkpoints are control points in the cell cycle where stop and go ahead signals regulate the cell cycle.
- They control transitions between the phases.
- They ensure that certain processes have been completed, e.g. DNA replication and presence of growth factors, before another phase starts.
- Three important checkpoints are G1, G2, and M checkpoints.
G1 Checkpoint (Restriction Point)
- Occurs at the end of G1 phase.
- Checks for the presence of growth factors, cell size, and DNA damage.
- Controls the transition to the S phase (DNA replication).
G2 Checkpoint
- Controls the transition from the G2 phase to the M phase (mitosis).
- Checks for DNA damage and DNA replication completion.
M Checkpoint (Metaphase Checkpoint)
- Controls the transition through the stages of mitosis.
- Checks for correct chromosome alignment in the mitotic spindle during metaphase.
The Cell Cycle Control System
- The cell cycle is regulated by a molecular control system.
- Cytoplasmic molecules regulate progress through the cycle.
- Three major checkpoints are G1, G2, and M.
- The G1, G2, and M checkpoints regulate transitions from one phase to the next based on internal and external signal input.
Mitogens (Growth Factors)
- Growth factors stimulate other cells to divide.
- An example is PDGF (platelet-derived growth factor) which stimulates fibroblast growth in a wound.
- Removal of mitogen will result in reduction in the cyclin-cdk levels; cells won't pass the restriction point R and won't replicate.
Cell Cycle Control by Cyclins/Cdks
- Specific cyclins and cyclin-dependent kinases (Cdks) control different steps in the cell cycle.
- Each phase has specific cyclin-cdk complexes.
MPF (Mitosis Promoting Factor)
- The signal that sends cells into mitosis is called MPF (Mitosis Promoting Factor).
- MPF consists of a mitotic cyclin (cyclin A or cyclin B) and cdk-1.
- MPF induces the progression from G2 to M phase by a variety of reactions including phosphorylation, inactivation of anaphase promoting complex, phosphorylation of nuclear lamina, and fragmentation of the nuclear envelope.
Negative Regulation of MPF activity by APC
- APC (Anaphase Promoting Complex) is an E3 ubiquitin ligase that inactivates mitotic cyclins and hence MPF during interphase.
- Proteolysis of mitotic cyclins at the end of mitosis leads to a reduction of MPF activity.
The TP53 Gene
- The TP53 gene encodes for the p53 protein.
- The p53 protein detects DNA damage, inducing G1-G2 arrest, apoptosis, or DNA repair.
- Over 50% of cancers contain mutations in the TP53 gene.
Density-Dependent Inhibition and Anchorage Dependence
- Density-dependent inhibition means crowded cells stop dividing.
- Anchorage dependence means most animal cells must be attached to a substratum to divide.
- Cancer cells do not exhibit density-dependent inhibition or anchorage dependence; they continue to divide well beyond a single layer leading to clumps of overlapping cells.
Cancer Cells: Loss of Cell Cycle Control
- Cancer cells do not respond normally to the body's control mechanisms.
- They make their own growth factors or have always-ON signaling pathways.
- They exhibit abnormal cell cycle control and form tumors
- Benign tumors are not invasive and contained within a particular site
- Malignant tumors are invasive and can spread to other organs (metastasis).
Malignant Tumors
- Malignant tumors invade surrounding tissues and export cancer cells to other parts of the body; forming secondary tumors.
Cancer Cells’ Characteristics
- Cancer cells have specific characteristics including resisting cell death, sustaining proliferative signaling, evading growth suppressors, inducing angiogenesis, and enabling replicative immortality.
Challenges to Cancer Treatment
- Cancer treatment challenges arise from the diverse physiological pathways and tissue specificities within tumours.
- Intratumoral, intermetastatic and interpatient heterogeneity further complicates treatment strategies.
- Precision Oncology is one approach used.
Precision Oncology
- The science of using a patient's genetics to create a treatment plan targeted to the particular molecular characteristics of a specific cancer.
- A rapidly developing research area.
SBA Example 1
- At which cell cycle phase is MPF (mitosis promoting factor) active?
- The correct answer is M phase.
SBA Example 2
- What does MPF consist of?
- The correct answer is Cyc-A/cdk-1.
External Signals (Summary)
- Growth factors stimulate cell division.
- Other external signals include density-dependent inhibition (crowded cells stop dividing) and anchorage dependence (cells must be attached to a substratum in order to divide).
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Description
Explore the intricate mechanisms of cell cycle regulation and the role of tumour suppressor genes such as RB1 and TP53. Understand how cyclin-dependent kinases (cdks) interact with cyclins to control cell division. This quiz covers essential concepts necessary for comprehending cell biology and cancer development.
