CELL CYCLE

Question 1

Normally, cells do not proliferate unless stimulated by what:

Answer 1

Extrinsic factors

Question 2

What are the potential decisions of a cell?

Answer 2

Quiescent (G0)
Proliferate
Differentiate

Question 3

If there is an overriding issue, what happens to the cell cycle?

Answer 3

Can be halted.

Question 4

A mixture of signals has to be integrated by the cell to make the decision as to what the cell is going to do. What in the cell nucleus makes the major decisions?

Answer 4

The cell cycle clock

Question 5

What mixture of signals has to be integrated by the cell for the cell to be able to make a decision?

Answer 5

Tyrosin kinase receptors
GCPR
TGF beta receptors
Integrins
Nutrient status

Question 6

What are the phases of the Cell Cycle?

Answer 6

G0 - quiescent state
G1 - CDK4/6 must associate with cyclin D’s. In this phase, the cell grows in preparation fro DNA replication and certain intracellular components undergo replication. At the end of G1, E cyclins must associate with CDK2 to progress into S phase.
S - A type cyclins bind with CDK2. S phase is where DNA is replicated. Later in S phase, A type cyclins bind with CDK1
G2 - B cyclins replace A cyclins binding with CDK1. In G2, there is rapid cell growth and protein synthesis.
M - B cyclins with CDK1 triggers mitosis

Question 7

What are the 2 major control factors of the cell cycle?

Answer 7

1. Binding of cyclins with cyclin dependent kinases

2. Cell cycle checkpoints

Question 8

Why does collapse of cyclin levels occur as the cell progresses through the cell cycle?

Answer 8

Degradation of specific cycle levels allows for unidirectionality.

Question 9

Why are D cyclins not the same as others?

Answer 9

They are controlled by extracellular signals.

Question 10

At what point does the cell cycle become cell autonomous?

Answer 10

At R point

Question 11

What are CDKs inhibited by?

Answer 11

CDK inhibitors

Question 12

What CDK inhibitors inhibit cyclin D?

Answer 12

p16INK4A
p15INK4B
p18INK4C
p19INK4D

Question 13

What CDK inhibitors inhibit other cyclins?

Answer 13

p57KIP2
p27KIP1
p21CIP1

Question 14

What are the cell cycle checkpoints?

Answer 14

R checkpoint - is the cell big enough, is the environment favourable, is there DNA damage.
G2 checkpoint - is all DNA replicated, is the cell big enough, is the environment stable?
M checkpoint - are all the chromosomes aligned on the spindle?

Question 15

What does DNA damage activate?

Answer 15

p53

Question 16

Describe G1/S Restriction Point Progression.

Answer 16

CDK4/6 and Cyclin D form a complex that phosphorylate pRb bound to E2F. Build up of Cyclin E binds to CDK2 which hyperphosphorylating pRb freeing E2F to transcribe driving the cell into S phase.

Question 17

When is DNA damage detected and what are the methods of repair.

Answer 17

The three checkpoints (G1, Entry to S phase, Entry to mitosis) are the sites of detection and arrest of the cell cycle.
There are two types of DNA repair in this case: non homologous end joining (G1) and homologous recombination (G2).

Question 18

How is the cell cycle arrested upon detection of DNA damage?

Answer 18

DNA damage detected
ATM (double stranded breaks) and ATR (for single stranded breaks) are activated and associate with the site of damage.
Other kinases are activated such as Chk1
This causes phosphorylation of p53
p53 activates p21 gene coding for CKI to arrest the cell cycle

Question 19

If DNA repair is incomplete then what occurs?

Answer 19

Apotosis will be triggered.

Question 20

What does the combination of p53 and Mdm2 mean for a cell?

Answer 20

Ubiquitylation and degradation of the cell

Question 21

If p53 is phoshporylated and as a result Mdm2 cannot bind to p53, what occurs?

Answer 21

active p53 binds to the regulatory region of p21 gene to transcribe for cyclin dependent kinase inhibitors to arrest the cell cycle.

Question 22

What is the purpose of the p21 gene being transcribed?

Answer 22

Arrest of the cell cycle to allow time for DNA repair to take place.
If repair cannot take place then apoptosis will take place.

Question 23

In G1, if the environment is not favourable or if there is an issue, what can occur?

Answer 23

The cell can make the decision to revert back to G0.

Question 24

Deregulation of R point decision making machinery accompanies what?

Answer 24

Formation of most types of cancer cells.

Question 25

What are the two important things that must occur is S phase?

Answer 25

1. The DNA must be replicated accurately to prevent mutations.
2. The DNA must only be copied once.

Question 26

What is licencing?

Answer 26

It is the process that occurs in G1 where inactive helicases are loading onto the replication origins, forming a PreRC complex.

Question 27

What happens to the PreRC complex after G1?

Answer 27

Helicases are activated in S phase by the S phase cyclin/CDK complexes and DNA is replicated.

Question 28

Is the cell cycle always the same?

Answer 28

No.
Throughout different types of cells ie fibroblasts, ESCs there are differences in cyclin levels. Even throughout life, the inclination of cell cycles change ie early cells are inclined to apoptose if there is an issue rather than arrest and repair.