The Cell Cycle Flashcards
Know the cell cycle
Starts with Mitosis, then G, then the S phase where chromosome replicate and then is the G2 phase.
Other than the S phase, we have interphase.
What are Mitogens
In order for the cell to grow or proliferate the cell has to have a signal, these are called mitogen, their receptors are called mitogen receptors.
Mitogens control cell cycling by acting on the G1 phase of the cell cycle
How does mitogens induce signaling
They do this by the growth factor mechanism. The receptor is phosphorylated at the intermembrane space, interacts with GRB2-SOS which then induces the RAS to binds to GTP which then induces the MAP kinases to initiate signaling
What does the MAP kinases do in this signaling
They induce gene regulatory proteins such as Myc. This is often over expressed in cancer. He said now we enter G1 phase
What happens before the cell goes to the next stage of cell cycle after G1
It checks if it has enough glucose and if it has the right ratio of ATP to AMP.
Fatty acid and glycogen synthesis is turned off.
What happens in G1
The cell basically gets bigger. This is the longest phase of the cell cycle. The following happens:
- Cellular energy level is high
- Increase protein synthesis
- Increase ribosome production
- Some organelle duplication
- Increase in cell size
What controls this desire to get bigger
Protein complex called mTORC. it is a big kinase complex but it also has the ability to sense nutrients. It senses free fatty acids and glucose in the environment and when there is plenty it is turned on and increases the rate of protein synthesis.
It activates ribosomes and elongation factors.
What happens after G1
We make DNA`
What are licensing factors
Proteins required to assemble the DNA helicase complex at ORC such as cdc6 and cdt1
What is necessary for the licensing factors to allow DNA replication
They have to be phosphorylated to be in active form and allow replication of the DNA
What happens to licensing factor? When are they made and when are they destroyed
They are made in early G1 phase and they are removed or destroyed in the M phase
What does geminin do
It binds to the licensing factors (cdt1) and inhibits them. It is highest in the S phase. Remember that the conc. of cdt1 increases in the G1 phase and keeps on increasing throughout the G1 phase and starts to decrease as the S phase starts.
Also the concentration of cdc6 increases as towards the end of G1 phase and keeps on increasing until the END OF S phase.
Geminin concentration increases in the S phase as it is an inhibitor of cdt1.
What protein complex forms during the S phase
The DNA is wrapped up in the S phase into a protein complex called the Cohesion complex. It wraps around the newly synthesised DNA. It acts as a cage.
When is the cohesion protein complex broken down
In mitosis
What happens in G2 phase
It check things, is DNA made? is it made correctly? Is the cell big enough?
If there are errors in DNA, they are corrected with the help of PARP.
How are cell cycles regulated
Cyclins, and with protein dependent cyclins kinases.
What are the positive and negative cell cycle regulators
Positive are cyclins, cyclin dependent protein kianses (CDK) and protein degradation.
Protein degradation actually promotes the cell to go the next cell cycle.
Negative regulators are Transcriptional repressors, CDK inhibitors and check points.
What are cyclins
Protein expressions cycle, they go up and down in a cell cycle, they are CDK substrates.
On the slide it said cyclins are important REGULATORS of CDK, their conc. goes up and down in a cell cycle
How is the G phase promotion regulated
In the cell initially there are CDK4 and CDK6 present that are not doing anything. The cell makes Cyclin D that binds to CDK 4 and 6. This activates 4 and 6 that go on and p’s things. This leads to promotion of the G1 phase. When the cell is ready for S phase there is a check point.
What is the check point for S phase
The cell makes Cyclin E which activates CDK 2. This commits the cell to replicate DNA and go on to the S phase. CDK2 phosphorylates p27 (I don’t think we need to know that).
What is involved in the progression of S phase
Degradation of cyclin E and making of cyclin A. Cyclin A also binds to CDK 2 and keeps it turned on during the S phase.
Cyclin A stimulates chromosome duplication (unlike cyclin E that initiated DNA replication)
What happens when you come near M phase
Cyclin A lasts through the G2 phase. As we near the M phase the cyclin A is degraded and we make another substance called Cyclin B. This activates CDK1. This allows entry into the M phase. it drives the cell through the M phase
What is the added check point of CDK1 that leads to mitosis
CDK1 when it binds to cyclin B is still off becuase it has inhibitory p’s on it. It is only activated after it is dephosphorylated by CDC25 (it is a phosphatase). This activated cdk1 leads to activation of more cdc25 which then activate more cdk1s (positive feedback loop).
What are the functions of CDK1.
There are 4.
- Assembly of mitotic spindle
- Chromosome condensation
- Nuclear envelope breakdown
- Actin cytoskeleton rearrangement
