Cell Replication

Question 1

what is cell cycle?

Answer 1

sequence of events in which a cell duplicates contents and divides into 2
cell will roughly double in size before dividing

Question 2

how long do embryonic stem cells take to divide?

Answer 2

30 mins

Question 3

hepatocytes?

Answer 3

1 year

Question 4

intestinal epithelial cells?

Answer 4

around 20 hrs

Question 5

which cell type(s) never divide?

Answer 5

neurones and cardiac myocytes

Question 6

stages of cell cycle?

Answer 6

G1, S, G2, M

Question 7

what is G0?

Answer 7

a quiescent phase where cells are dormant and not dividing
carries out all cellular functions though
this happens in absence of stimulus

Question 8

e.g. of G0 cells?

Answer 8

neurons, skeletal muscle, hepatocytes

Question 9

G1 checkpoint?

Answer 9

before S phase, checks for whether cellular environment is favourable

Question 10

G2 checkpoint?

Answer 10

is all DNA replicated?
is all DNA damage repaired?

Question 11

mitosis checkpoint?

Answer 11

are all chromosome properly attached to mitotic spindle?

Question 12

why/how do cells ever leave G0?

Answer 12

response to growth factors (tell a cell to move from G0 into G1)

signal amplification

signal integration

Ras/Raf/MEK (protooncogenes)

Question 13

c-Myc?

Answer 13

stimulated by growth factor
c-Myc promotes G0 to G1 transition
=oncogene, overexpressed in many tumours

Question 14

Cdks?

Answer 14

cyclin dependent kinase
controlled by phosphorylation/ dephosphorlyation
allows exquisite control of events
only active when CYCLIN is bound

Question 15

which 3 amino acids can be phosphorylated and why?

Answer 15

serine, threonine, tyrosine
they contain -OH group

Question 16

nomenclature of cyclins?

Answer 16

their concentrations fluctuate within cell cycle

Question 17

cell cycle entry requirements?

Answer 17

growth factor –> C-Myc –> cyclin D –> cyclin D/Cdk 4/6 complex

Question 18

protein kinase cascades?

Answer 18

often the protein regulated by a kinase is a kinase and so on… this creates a protein kinase cascade
leads to:
signal amplification
diversification
OPPORTUNITY FOR REGULATION

Question 19

kinases?

Answer 19

phosphorylate another molecules, e.g. a protein and thereby activating it

Question 20

phosphatases?

Answer 20

reverses phosphorylation, deactivating a kinase

Question 21

is expression of cyclins transient or are they present throughout cell cycle?

Answer 21

transient, they’re expressed at specific points in cell cycle
this is in contrast to Cdks which are present throughout cell cycle

Question 22

how are Cdks regulated?

Answer 22

phosphorylation
interaction with cyclins

Question 23

steps of Cdk activation

Answer 23

1. inactive cdl
2. cyclin binds, inactive cyclin-Cdk complex
3. an activating protein phosphatase gets rid of the inhibitory phosphates, thereby activating the complex (i.e. sequential phosphorylation and dephosphorylation)

Question 24

positive feedback?

Answer 24

drives cell cycle forward

Question 25

how are cyclins turned off?

Answer 25

ubiquitination = method to degrade proteins
in this example we are degrading cyclin, thus inactivating Cdk

Question 26

sequential?

Answer 26

one Cdk will activate the cyclin which is required for the next phase
e.g. Cdk4/6 stimulates expression of cyclin E
this gives DIRECTION and TIMING to cycle

Question 27

Rb?

Answer 27

=retinoblastoma (present in all nucleated cells)
a molecular ‘brake’
it’s a tumour suppressor, so when it’s missing/inactive it can cause tumours e.g. a retinal tumour

Question 28

function of Rb?

Answer 28

acts as a brake on cell proliferation
sequesters a transcription factor in inactive form
the TFs cannot turn on genes needed for cell cycle progression e.g. DNA polymerase, thymidine kinase

Question 29

how can the brake be released?

Answer 29

activation of intracellular signalling leads to production of G1-Cdk and G1/S-Cdk complexes

these phosphorylate Rb, inducing the inactivation of Rb and release of the TF

target genes such as those which control enzymes such as DNA polymerase and thymidine kinase can now be activated

Question 30

what specific example of TF?

Answer 30

E2F

Question 31

release of E2F allows what?

Answer 31

cell cycle progression

Question 32

p53?

Answer 32

a tumour suppressor
arrests cells with DNA damage in G1
protein kinases phosphorylate p53, activating it

Question 33

p21 gene

Answer 33

induced by active p53
=another molecular brake
inhibitor of cyclin:Cdk complexes
this makes sense as cyclin:Cdk complexes cause activation of G1 and the cell cycle

Question 34

examples of oncogenes

Answer 34

EGFR/HER2: over-expressed in breast cancers

Ras: mutationally activated in many cancers

Cyclin D: overexpressed in 50% of breast cancers

C-Myc: overexpressed in many tumours

Question 35

tumour suppressor examples?

Answer 35

Rb - loss of function mutations in 80% of small cell lung cancers
p53 - loss of function mutations in over 50% of all cancers

Question 36

what is p21?

Answer 36

cyclin-dependent kinase inhibitor, can inhibit all Cdks