Cell Cycle

Question 1

What is the process from zygote to complex system?

Answer 1

Zygote, blastocyst, post implantation epiblast, gastrulation, complex systems made

Question 2

What causes proliferation? What can stop proliferation

Answer 2

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.

Question 3

What causes proliferation (cell growth) and quienscence (non proliferative state of the cell)

Answer 3

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.

Question 4

What are the phases of the cell cycle. Starting from G1? And what controls the phase?

Answer 4

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

Question 5

What are the two controls of the cell cycle?

Answer 5

CDKs and different cyclins

And also checkpoints.

Question 6

A summary of when cyclin E, A, B are present?

Answer 6

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

Question 7

What decreases the levels of cyclin at different stages of the cell cycle

Answer 7

Degradation caused by ubiquitination

Question 8

What causes the fluctuation of cyclin D concentration (found in G1 phase)?

Answer 8

Growth factors + integrin mediated extra cellular matrix attachment increase cyclin D concentration

Removal of growth factors sees a rapid decrease in cyclin D1 levels

Question 9

Comparison of how D cyclins are controlled in comparison to the other cyclins in the cell cycle?

Answer 9

D cyclins are controlled by EXTRACELLULAR signals

Other cyclins are controlled by INTRACELLULAR signals

Question 10

What happens once you go from G1 to the restriction point (note this is also a part of g1)

Answer 10

Cyclin D becomes cyclin E

Once you reach this point you are committed to mitosis.

Question 11

What also regulates CDKs?

Answer 11

CDK inhibitors. There are 7 proteins which does this.

Question 12

What happens once you reach the restriction point in G1 phase?

What are the three questions you ask?

Answer 12

Is the cell big enough?

Is the environment favourable (Are there enough nutrients)

Is DNA damaged?

If all fine continue to S phase

Question 13

What three questions should you ask yourself at the Second checkpoint in the cell cycle?

Answer 13

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.

Question 14

What happens at the 3rd cell cycle checkpoint?

What two questions do you ask?

Answer 14

This is the metaphase checkpoint

You ask:
- are all chromosomes aligned on the spindle.

Question 15

So remember the checkpoints check for DNA damage.

So when can DNA be damaged in the cell cycle?

Answer 15

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)

Question 16

What happens in S phase of the cell cycle?

Answer 16

This is when DNA is being synthesised

This is when DNA may be damaged

Question 17

What may happen as you enter M phase - mitosis

Answer 17

Chromosomes may be non disjunctional

They haven’t attach to spindles or separate incorrectly

Question 18

What are the different methods of repairing the DNA of the cell cycle?

Answer 18

G1 repair - this sees non homologous ends joining

G2 repair - this sees homologous recombination.

Question 19

What is one method of dealing with DNA damage?

Answer 19

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)

Question 20

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

Answer 20

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.

Question 21

What happens when the p21 (inhibitory kinases) become activtaed?

Answer 21

They stop the G1 phase / S phase cyclin dependent kinases from working

The cell cycle cant progress

So DNA is then repaured

Question 22

What happens if DNA repair isnt possible?

Answer 22

Then cell apoptosis occurs

Question 23

At G1 the decision for the cell to remain quiescence (so not divide) or proliferates occurs

What causes quiescence and what causes proliferation?

Answer 23

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

Question 24

What are the problems in S phase?

Remember this is when the cell cycle is replicated.

Answer 24

The DNA has to be replicated accurately to prevent

The DNA must only be copied once

Question 25

What happens in G1 phase in terms of DNA helicase?

Answer 25

The inactive DNA helicase is loaded onto the replication origins (remember chrosome rep lecture)

This forms a preRC in a process called licensing

Question 26

What happens in S phase in terms of DNA helicase?

Answer 26

In S phase DNA helicase is activated and DNA is unowrd

DNA is replicated

Question 27

What triggers chromsome separation in M phase?

Answer 27

M - CDK

Question 28

What replication issue cans you have during S phase DNA replication? Why might this occur?

What DNA repair can happen in s phase?

Answer 28

The DNA forks may stall, which causes the DNA damage response

This can happen when nucleotides in the cell deplete, so replication has to stop

Repair in s phase can happen to the DNA at parts which have a mistake. This can be detected and the DNA can be resected and filled back in

Question 29

How do the cell change during the cell cycle?

Answer 29

In embryonic stages DNA damage would cause apoptosis

Whereas DNA damage in later stages leads to DNA repair.

Question 30

Remember cyclins other than D cyclins

Answer 30

Are regulated by CKI

Question 31

What is important to note about mouse and human stem cells

Answer 31

Their levels of cylin D or E differ and show up in different pHASES.

Just remember in any cycles shown, if the cylin kinases arent in the correct amounts to what you have been taught. Then you know the cell must be mutated or something.