28 Questions
What is the main consequence of failure to attach spindle fibres correctly during cell division?
Failure to separate chromosomes
What is the primary function of the G2 checkpoint?
To prevent mitosis until DNA replication is completed
What is the most critical process during the cell cycle?
DNA replication
What is the molecular mechanism that restricts DNA replication to once per cell cycle?
The action of MCM (mini-chromosome maintenance) proteins
When does the licensing process for DNA replication occur?
During G1 phase
What is the significance of the difference in CDK activity between the two stages of the cell cycle?
It ensures that DNA replication occurs only once per cycle
What is the role of p53 in response to DNA damage at the G1 checkpoint?
Prevents cell cycle progression
What happens if there is a loss of function mutation in the p53 gene in response to DNA damage?
G1 arrest is prevented
Why are p53 mutations considered significant in cancer development?
They prevent G1 checkpoint arrest
Which protein is transcriptionally activated by p53 to arrest cell division at the G1 phase?
p21
How does an increase in p53 protein levels affect cell cycle progression during G1 checkpoint arrest?
It promotes G1 arrest
What is the primary function of p21, a member of the Cip/Kip family of Cdk inhibitors?
Inhibiting Cdk2 complexed with cyclin E and cyclin A, preventing both the G1-S transition and progression through S phase
Which of the following statements about Cdk regulation is correct?
Cdk activity is regulated by a combination of cyclin association, phosphorylation, and Cdk inhibitor binding
What is the primary function of the Ink4 family of Cdk inhibitors?
Inhibiting Cdk4 and Cdk6 complexed with cyclin D, preventing passage through the G1 checkpoint
Which of the following is NOT a mechanism of Cdk regulation mentioned in the text?
Ubiquitination and proteasomal degradation of Cdks
What is the primary function of cell cycle checkpoints?
Ensuring that incomplete or damaged chromosomes are not replicated and passed on to daughter cells
What prevents re-licensing of DNA in the cell cycle?
Phosphorylation of licensing factors
When does the MCM complex act as a replicative helicase?
During DNA replication
What happens to Geminin at the end of M phase?
It is degraded
Which proteins are activated to initiate DNA replication in a new cell cycle?
CDKs and DDK
What role does CDK-dependent phosphorylation play in DNA replication?
Inhibiting chromatin binding of licensing factors
When can DNA be licensed for replication?
At the end of M-phase with low CDK activity
What is the primary function of cyclin-dependent protein kinases (Cdks)?
To regulate the cell cycle by phosphorylating cellular proteins
Which of the following is NOT one of the main types of cyclins mentioned?
Cyclin C
What is the name given to the complex formed by Cdk1 and cyclin B?
Maturation Promoting Factor (MPF)
Which of the following is NOT a mechanism for controlling CDK activity?
Constitutive activation of CDKs throughout the cell cycle
What is the primary target of the Maturation Promoting Factor (MPF) during mitosis?
Lamins, condensins, and microtubule-associated proteins (MAPs)
What is the significance of the cyclical activation and deactivation of protein kinases in the cell cycle?
It allows for flexible control and checkpoint regulation of the cell cycle
Study Notes
Cell Cycle Regulation
- Failure to attach spindle fibers correctly would result in failure to separate chromosomes
- G2 checkpoint prevents initiation of mitosis until DNA replication is completed in response to DNA damage, allowing time to repair DNA
- G2 arrest: DNA replication is the most critical process, and all DNA should be replicated
DNA Replication Licensing
- Mechanism that restricts DNA replication to once per cycle: action of MCM (mini-chromosome maintenance) proteins (licensing factor) binds to Origin Replication Complex (ORC) proteins, initiating DNA replication
- Licensing process is accomplished by the step-wise assembly of initiator proteins on origin DNA
- ORC is probably present on chromatin throughout a cell cycle and acts as a landing pad for Cdc6/18 and Cdt1, which load the MCM complex onto the chromatin, establishing licensing
Cell Cycle Checkpoints
- DNA damage arrests cell cycle at G1 checkpoint, allowing time to repair damaged DNA before S phase
- p53 is a tumor suppressor gene that senses DNA damage and induces p21 expression, arresting cell division at G1
- p53 mutations are the most common genetic alterations in human cancers
Cdk Regulation
- Mechanism of Cdk Regulation: association with cyclins, cyclin synthesis and degradation, activating phosphorylation by CAK, inhibitory phosphorylation by Wee1, and activating dephosphorylation by Cdc25 protein phosphatase
- Association with Cdk inhibitors: Two Families of Cdk inhibitors, Cip/Kip family and Ink4 family
- Cdk-cyclin complex triggers passage through different stages of the cell cycle
Cyclins and Cdks
- Types of Cyclins: Cyclin D (G1 cyclin), Cyclin E (S-phase cyclin), Cyclin A (S-phase and mitotic cyclin), and Cyclin B (mitotic cyclin)
- Types of Cdks: Cdk4 (G1 Cdk), Cdk2 (S-phase Cdk), and Cdk1 (mitotic Cdk)
- The complex of Cdk1 and Cyclin B is called Mitosis Promoting Factor (MPF)
Cell Cycle Control System
- Cell cycle is driven by protein synthesis and degradation
- CDK activity is controlled by positive regulation by cyclin protein levels, inhibitory phosphorylation of the kinase subunit, and multiple levels of regulation
- Cyclical activation of protein kinases and cell cycle progression
Test your knowledge about cyclin, Cyclin-Dependent Protein Kinase (Cdks), and their roles in regulating the cell cycle. Learn about the catalytic functions of Cdks, the different types of cyclins, and how Cdk-cyclin complexes trigger cell cycle progression.
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