Cell Cycle Flashcards
What is the process from zygote to complex system?
Zygote, blastocyst, post implantation epiblast, gastrulation, complex systems made
What causes proliferation? What can stop proliferation
This is cause when normal cells are stimulated by extrinsic factors.
Note multiple different signals are needed to make a cell proliferate, remain quiescent (so undecided) or differentiate
Extracellular signals can stop differentiation.
What causes proliferation (cell growth) and quienscence (non proliferative state of the cell)
These are causes by a network of proteins inside the cell
They detect signals from inside and out of the cell which helps decide the cells fate.
What are the phases of the cell cycle. Starting from G1? And what controls the phase?
G1 phase
- controlled by CDK4 and CDK6 (kinases)
Restriction point (part of G1 phase) - this is when E type cyclins associate with CDk2. This interaction causes substrates to be phosphorylated allowing for entry into S phase
S phase:
- A cyclins now associate with CDK2 instead of E cyclins
- S phase progresses
- you then later get A cyclins associating with CDk1 (CDC)
G2 phase:
- in this phase B cyclins replace A cyclins in order to bind to CDk1
M phase
- b cyclins associated with CDK1 cause mitosis
Gzero to G1 (when the circle is about to complete)
- this process is mediated by CDK3
What are the two controls of the cell cycle?
CDKs and different cyclins
And also checkpoints.
A summary of when cyclin E, A, B are present?
Cyclin D
- high during G1 until the R point
Cyclin E
- low amounts in G1
- rapid increase after the R point
Cyclin A
- levels increase as you enter S phase
Cyclin B
- this increases as you anticipate mitosis
- so in G2 and M phase
Remember you then enter G zero with no cyclin
What decreases the levels of cyclin at different stages of the cell cycle
Degradation caused by ubiquitination
What causes the fluctuation of cyclin D concentration (found in G1 phase)?
Growth factors + integrin mediated extra cellular matrix attachment increase cyclin D concentration
Removal of growth factors sees a rapid decrease in cyclin D1 levels
Comparison of how D cyclins are controlled in comparison to the other cyclins in the cell cycle?
D cyclins are controlled by EXTRACELLULAR signals
Other cyclins are controlled by INTRACELLULAR signals
What happens once you go from G1 to the restriction point (note this is also a part of g1)
Cyclin D becomes cyclin E
Once you reach this point you are committed to mitosis.
What also regulates CDKs?
CDK inhibitors. There are 7 proteins which does this.
What happens once you reach the restriction point in G1 phase?
What are the three questions you ask?
Is the cell big enough?
Is the environment favourable (Are there enough nutrients)
Is DNA damaged?
If all fine continue to S phase
What three questions should you ask yourself at the Second checkpoint in the cell cycle?
The second checckpoint in the cell cycle isnt in S phase!
It is in G2 phase
You should ask:
- is all DNA replicated
- is the cell big enough
- is the environment favourable
If it is then go into the next phase, M phase.
What happens at the 3rd cell cycle checkpoint?
What two questions do you ask?
This is the metaphase checkpoint
You ask:
- are all chromosomes aligned on the spindle.
So remember the checkpoints check for DNA damage.
So when can DNA be damaged in the cell cycle?
G1 phase. (Checked by the Restriction point)
S phase (checked at the G2 checkpoint)
During late G2 and M phase (detected by the M checkpoint)
What happens in S phase of the cell cycle?
This is when DNA is being synthesised
This is when DNA may be damaged
What may happen as you enter M phase - mitosis
Chromosomes may be non disjunctional
They haven’t attach to spindles or separate incorrectly
What are the different methods of repairing the DNA of the cell cycle?
G1 repair - this sees non homologous ends joining
G2 repair - this sees homologous recombination.
What is one method of dealing with DNA damage?
ATM / ATR get activated and associate with the site of DNA damage
ATM / ATR will activate other kinases to block the cell cycle
P53 is phosphorylated and stabilised and turns on p21 (which is an inhibitory kinase)
What causes the p53 protein (which is an inhibitory protein) to become phosphorylated and then activated in order to activate the p21 gene which codes for the inhibitory CDK?
Remember this is in reference to detecting DNA damage
So remember p53 is a inhibitory protein which detects DNA damage]
Usually attached to p53 is a Mdm2. This normally causes the p53 to degrade by ubiquitination
But when there is DNA damage the phosphorylation of p53 means Mdm2 is removed from the p53 and the p53 isn’t degraded
The p53 can then go onto activate the p21 gene to make inhibitory kinases to stop the cell cycle.
What happens when the p21 (inhibitory kinases) become activtaed?
They stop the G1 phase / S phase cyclin dependent kinases from working
The cell cycle cant progress
So DNA is then repaured
What happens if DNA repair isnt possible?
Then cell apoptosis occurs
At G1 the decision for the cell to remain quiescence (so not divide) or proliferates occurs
What causes quiescence and what causes proliferation?
Quiescence
- is caused when growth factors are REMOVED from the cells before 80-90% of the G1 phase has complete
- If this happens the cell goes from G1 to Gzero
Proliferation:
- If 80 - 90% of the cell cycle has completed? Then proliferation occurs
- removal of serum and growth factor has no effect. The cell cycle continues
What are the problems in S phase?
Remember this is when the cell cycle is replicated.
The DNA has to be replicated accurately to prevent
The DNA must only be copied once
