Cell cycle Flashcards
What is the G1 phase?
A growth period preceeding DNA synthesis
What is the is the S phase
DNA synthesis phase
What is the G2 phase?
Second period of growth where there is x2 DNA
Where are the checkpoints located?
G1/S and G2/M
What is the G1/S checkpoint called? What is the cell doing?
The restriction point
Checking to see if division is favorable
At the G2/M checkpoint, what is the cell doing?
Checking to make sure that all of the DNA has been replicated
What is the cell doing at the metaphase/anaphase transition point?
Evaluating all of the chromosomes to ensure that they are attached to the mitotic spindle
What is the DNA damage checkpoint? When does it occur?
Check to ensure there is no damaged DNA in the cell.
All the time.
Progress through the cell cycle is driven by what family of enzymes? What proteins?
Cyclin dependent kinases, which are regulated by cyclins
What cyclins/ CDKs are present in the M phase?
Cycline A, B and CDK1
What cyclins/ CDKs are present in the Mid G1 phase?
Cycline D and CDK4, CDK6
What cyclins/ CDKs are present in the late G1 phase?
Cyclin E and CDK2
What cyclins/ CDKs are present in the S phase?
Cyclin A and CDK 2
How are cyclins degraded?
By ubiquitin dependent proteolysis
What does the anaphase promoting complex do in the last part of M phase?
Ubiquinates cyclin B, marking it for destruction and triggering G1 phase
How are CDKs regulated (generally)?
de/phosphorylation and CDK inhibitors
What are mitogenic signals?
Tissue specific growth factors
Most differentiated cells are in what stage?
G0
Do cell-cell interactions promote or inhibit cell division?
Inhibit
Do cell-ECM interactions promote or inhibit cell division?
Promote
What is the action of c-Fos?
Stimulate the transcription of delayed response genes
What are early response genes?
Genes that are stimulated very soon after the addition of growth factors
What do delayed response factors encode?
Mid-G1 cyclins and CDKs
Late G1 cyclins and CDKs
What type of kinase is the growth factor receptor?
Tyrosine kinase
What is the order of the assembled complex that binds to the growth factor receptor?
GRB2, Sos, and Ras
What type of cascade is the growth factor cascade?
MAP-kinase cascade
What does Sos do?
Promotes the phosphorylation of Ras to the GTP bound form
What does Ras activate? What class is this molecue?
Raf–a protein kinase
What is the action of Raf?
phosphorylates MAP kinase kinase
What is the action of MAP kinase kinase? What does that molecule do?
Phosphorylates MAP kinase, which enter the nucleus and activates c-Fos transcription
True or false: growth factors are still needed after c-Fos is activated?
False
What is the target for CDK4/6 complex?
Rb protein–they phosphorylate this
What are Rb proteins?
Proteins that bind to, and inhibit E2F proteins
What are E2F proteins?
Transcription factor that activates the late G1 cyclin, S phase cyclin, and the S-phase CDK
What is the function of the E2F/Rb complex?
Recruit HDACs–inhibit DNA transcription
What does phosphorylation of the Rb/E2F complex by CDK4/6 complex do?
Separates Rb ad E2F, allowing E2F to function
Cyclin E and CDK2 are generated by E2F. What does this complex do?
Autostimulates E2F disassociation from Rb
What is the action of INK4 proteins?
Specificially inhibit CDK4/6 activity by competing with cyclin D for binding with CDK4/6.
What is the action of p27KIP1?
Inhibits cyclin A-CDK2 (the cyclin/CDK in S phase) by binding the cyclin A/CDK2 complex
Phosphorylation of p27KIP1 does what?
Disassociates p27KIP1 from the cyclin A/CDK2 complex, allowing the complex to phosphorylate (activate) the origins of replication for DNA synthesis
What does the CyclinA/CDK2 complex do?
Phosphorylates the origins of replication and begins the synthesis of DNA
When is cyclin A present? Cyclin B?
A from the beginning of S
B from late in S
CDK1/cyclin A (or B) are inactivated until what time? How are the activated? What do they do?
Activated after DNA has been fully replicated
Phosphorylation actives them
Activate mitosis
What is the function of ATM?
It detects replication forks, activating another kinase to prevent dephosphorylation of cyclin/CDK1
What complex is inhibited when kinetochores are not associated with a spindle fiber?
Anaphase promoting complex
What is the action of p27KIP1 ?
inhibition of the cyclinA/CDK2 complex (which activates S phase)
What is the action of p53 protein?
Activates p21CIP1.
What is the action of p21CIP1?
Inhibits BOTH cyclin/CDK1 and cyclin CDK2 commplexes, completely stopping progression of the cell.
Assume there is a double stranded break in DNA. What protein will detect this? Describe the signalling pathway leading to inhibition of further cell progress (Hard, 3 steps in the pathway).
- ATM/ATR detect DNA break, activate p53
- p53 activated p21^KIP1
- Inhibition of CDK2/cyclin E, and CDK1/cyclinA
Defects in genes that encode ATM/ATR leads to what disease?
Ataxia telangiectasia
