Cell Cycle Flashcards
What are the four coordinated processes of the eukaryotic cell cycle?
- Cell growth
- DNA replication
- Distribution of replicated chromosomes to daughter cells
- Cell division
Name the four phases of the cell cycle.
- M Phase - Mitosis (nuclear division) & Cytokinesis (cytoplasmic division)
- G1 Phase - cell active and growing
- S Phase - DNA replication
- G2 Phase - preparation for mitosis
What is the G0 phase and when do cells enter it?
Cells that are not dividing exit the cell cycle and rest in G0
How long does a typical cell cycle last in rapidly dividing human cells?
- G1 - 11 hours
- S - 8 hours
- G2 - 4 hours
- M - 1 hour
How is the cell cycle in eukaryotes regulated?
Cyclin Proteins and Kinase Complexes: Cycle-Dependent Kinases (CDKs)
What is the M phase kinase?
Complex of CDC-2 and Cyclin B
What is the regulatory subunit for the CDC-2 protein kinase?
Cyclin B
What is the role of G1/S cyclins?
Activate CDKs in late G1 and trigger progression through start/restriction point
What is the role of S cyclins?
Bind CDKs after START and trigger DNA synthesis
* Remain elevated until mitosis
What is the role of M cyclins?
CDKs that stimulate entry into mitosis at G2/M checkpoint
What is the role of G1 cyclins?
Govern activity of G1/S cyclins
How are CDK/Cyclin complexes activated?
Phosphorylation of conserved Thr-160 residue
How is degradation of cyclins mediated?
By ubiquitin ligases
How is Cdk1 (CDC2) activity regulated during the cell cycle?
What role does phosphorylation play in Cdk regulation?
What is the restriction point (START in yeast) in the cell cycle?
Name three major cell cycle checkpoints.
What happens if the environment is not suitable at a checkpoint?
How do checkpoints ensure genomic integrity?
What factors can trigger cell cycle arrest at checkpoints?
What are CKIs and how do they function?
CDK Inhibitors
*Bind to CDK/Cyclin complexes
* Induces conformational change
* Affects active site of CDK
Name three families of CKI proteins.
- P16
- P21
- P27
How does p21 inhibit the cell cycle?
- Binds to a variety of CDK-Cyclin complexes
- Supresses G1/S-CDK and S-CDK activities following DNA damage
What is the specific role of p16 in cell cycle regulation?
Specifically arrests cells in G1by binding to complexes of CDK-4 and CDK-6 with Cyclin D
What is the role of the Rb protein in cell cycle control?
Key substrate of the CDK-4/Cyclin D complex (G1/S transition)
How does Rb regulate E2F transcription factors?
Rb is under-phosphorylated in G0 and G1, and binds to E2F transcription factors
How does Rb phosphorylation affect E2F-regulated gene expression?
- Phosphorylation of Rb by CDK-4/Cyclin-D causes dissociation of Rb from E2F
- E2F target genes able to be transcribed
- DNA synthesis
Why is Rb considered a tumour suppressor gene?
Slows down cell cycle
How do growth factors influence the cell cycle?
Control progression through restriction point in G1
What is the function of immediate early genes in cell cycle entry?
How does Myc contribute to cell cycle progression?
*
How does DNA damage affect the cell cycle?
What is the role of ATM kinase in the DNA damage response?
How does p53 contribute to cell cycle arrest after DNA damage?
What is the relationship between p53 and p21 in the context of DNA damage?
How can oncogene activation or p53 activation lead to different cellular outcomes?
How is cell growth coordinated with cell division?
What is the role of the PI3-kinase/mTOR pathway in cell growth?
How do growth factors stimulate nutrient uptake and protein synthesis?
What factors influence the balance between cell growth and division?
How do cells ensure they reach an appropriate size before dividing?
How does protein degradation contribute to cell cycle control?
What is the role of ubiquitin ligases in cyclin degradation?
How does the anaphase-promoting complex (APC) contribute to cell cycle progression?
Why is cyclin degradation important for cell cycle exit?
How does proteolysis of CKIs affect cell cycle progression?
How does the cell cycle differ between budding and fission yeast?
What model systems are used to study the cell cycle, and what are their advantages?
How do early embryonic cell cycles differ from those of somatic cells?
What techniques are used to study DNA synthesis in cell cycle research?
How is flow cytometry used to analyse cell cycle progression?
What is the purpose of checkpoints in the cell cycle?
Ensure that incomplete or damaged chromosomes are not replicated and passed on to daughter cells
What happens at the M phase checkpoint?
Anaphase is blocked if chromatids are not properly assembled in mitotic spindle
What happens at the G1 phase checkpoint?
*DNA damage checkpoint
* Entrance into S phase is blocked if the genome is damaged
What happens at the S phase checkpoint?
*DNA damage checkpoint
* DNA replication is halted if genome is damaged
What happens at the G2 phase checkpoint?
Entrance into M phase is blocked if DNA replication is not completed
Which phase in the cell cycle is the Restriction Point located?
G1
What is the Restriction Point in the cell cycle?
The period during which cells are responsive to mitogenic GFs and TGF-β