Cell Replication

Question 1

What happens during the M phase of cell cycle

Answer 1

nuclear division and cytokenesis

Question 2

what happens during the interphase

Answer 2

duplication of DNA,organelles and protein synthesis

Question 3

phases in Interphase

Answer 3

G0(quiescent state) , G1 (decision where it decides if there is enough nutrients or growth factors) , S phase, G2(check)

Question 4

How/why do cells ever leave G0? What are the signalling cascades involved ?

Answer 4

• Response to extracellular factors(growth factors stimulate entry from G0 into the G1 phase) signalling environment is fine. Stimulates tyrosine kinase enzymes inside
• Signal amplification
• Signal integration/modulation by other pathways
• oncogenes

Question 5

what is c myc

Answer 5

growth factor signalling pathways induce expression of cmyc.

cmyc promotes G0 to G1 transition.

It is an oncogenes which is overexpressed in many tumours

Question 6

what are cyclin dependent kinases

Answer 6

‘kinases’phosphorylate molecules such as serine/tyrosine and threonine as they all have OH groups.
Present in proliferating cells but only active when cyclin is bound

Question 7

How are the kinases turned on and off

Answer 7

turned on by phosphorylation and off by phosphatases

Question 8

Process of activating Cdks

Answer 8

1) Cdks are always present
2) cyclin transientrly produced and binds to cdK but Cdk is still inactive
3) Phosphorylation by multiple kinases (now has both inhibitor and activating phosphate but still inactive)
4) Phosphatase removes inhibitory phosphate and cdk now active. Active CDK stimulates positive feedback by activating more phosphatases

Question 9

how are cyclins turned off

Answer 9

ubiqutination - ubiquitone molecules attach to cyclin and cyclin is degraded by proteosomes and is degraded to amino acids

Question 10

how is a one way system mantained in the cell cycle

Answer 10

Cdks become sequentially active and stimulate synthesis of genes for the next phase and cyclins - gives direction and timing to cycle

Question 11

how does a retinoblastoma work

Answer 11

works when the retinoblastoma protein is missing or inactive. It is normally a tumour supressor.

Question 12

How does Rb work

Answer 12

Active Rb sequesters a TF in an inactive form.
The TFs cannot turn on genes needed for cell cycle progression.

Activation of intracellular signalling leas to production of the various CdK complexes which can phosphorylate Rb and induces the inactivation of Rb and release of TF. Target genes such as DNA polymerase and thymidine kinase now activated

Question 13

p53

Answer 13

1) double stranded DNA broken . P53 recognises that double stranded break and activates the protein kinases that phosphorylate p53, stabilising and activating it
2) active p53 binds to regulatory region of p21 gene
3) p21 mRNA translates to Cdk inhibitor protein and so cyclin is blocked from being activated and so cell cycle cannot continue

Question 14

Which cells never replicate

Answer 14

Neurones and cardiac myocytes

Question 15

What factors affect is a cell needs to divide

Answer 15

Embryonic vs adult cell
Complexity of system
Necessity for renewal
State of differentiation 
Tumour cells

Question 16

Why is mitosis the most vulnerable part of the cell cycle

Answer 16

Cells more easily killed (irradiation; heat shock; chemicals)
2. DNA damage cannot be repaired
3. Gene transcription; no new mRNA or proteins
Metabolism
Its the part where the cell actually divides

During replication , DNA is less condensed and therefore protected to a lesser degree from toxic agents

Question 17

The different check points in the cell cycle

Answer 17

G1 checkpoint - is the environment ( nutrients and growth factors) favourable to enter S phase/ is there damaged DNA
S phase checkpoint - damaged or incompletely replicated DNA
G2 checkpoint - is all the DNA replicated and is all DNA damage repaired so that the cells can enter mitosis
Checkpoint in mitosis; are all the chromosomes properly attached to the mitosis spindle for the duplicated chromosomes apart

Question 18

What are the 3 main phases of the cell cycle

Answer 18

1) cell growth and chromosome replication
2) chromosome segregation
3) cell division

Question 19

Which cyclin CDK complex promotes the transition from G0 to S phase

Answer 19

Cyclin D - CDK 4/6 complex

Question 20

How long does it take for for the cell to progress from S phase to mitosis

Answer 20

Between 12 to 24 hours, different length of cell cycle in different animals is due to the different amount of times spent in the G0 phase

Question 21

Cyclin dependent kinase activity is regulated by

Answer 21

• interaction with the cyclin s
• phosphorylation

Due to multiple steps and actually activating the cycle and CDK complex the process can be tightly regulated so each step of phosphorylating the CDK complex means that there is an extra stage of regulating the process

Question 22

What is a mitogen

Answer 22

Basically a growth factor and something that stimulates cell proliferation

Question 23

Which phase of the cell cycle does p53 work in

Answer 23

P53 arrests cells with damaged DNA in G1 phase

Question 24

Why is p53 constantantly made and then degraded

Answer 24

So that if DNA damage is detected, it can immediately be halted instead of having to wait for further p53 to be produced

Question 25

Examples of oncogenes

Answer 25

EGFR/HER2 - metastatic breast cancer
Ras- mutationally activated in many cancers
Cyclin D1 - breast cancers
C-Myc- over expressed in many tumours

Question 26

Tumour suppressors

Answer 26

Rb
p53

( loss of function mutations mostly )