Cell replication

Question 1

Which cells in the human body never divide?

Answer 1

cardiac myocytes + neurons

Question 2

What are the steps of cell replication?

Answer 2

Interphase (G1, S, G2) then mitosis (prophase, metaphase, anaphase, telophase, cytokinesis)

Question 3

What is G0 phase?

Answer 3

G naught = quiescent phase, without a stimulus, cells go into G0 after G1, instead of S phase

Cells remain busy, not dormant

Question 4

What does the cell monitor in the external environment before going into DNA replication, during G1 phase?

Answer 4

nutrients & growth factors

Question 5

What will the cell do if it detects DNA damage?

Answer 5

pause and repair DNA or undergo apoptosis

Question 6

How do cells leave G0?

Answer 6

tyrosine kinase receptors (growth factors bind to gf receptors) and signal different pathways- increase protein synthesis & protein degradation decreased leading to cell growth (double in size)

growth factor signaling pathway leads to the expression of c-Myc which promotes cyclin expression and hence the activation of Cdks so that: G0 -> G1 then S, etc

Question 7

What is c-Myc?

Answer 7

transcription factor that stimulates the expression of cell cycle genes

oncogene = overexpressed in many tumours

Question 8

What are the amino acid residues on kinases (incl. cyclin dependent kinases?)

Answer 8

Serine/Threonine/Tyrosine

-all have OH groups that could be phosphorylated

Question 9

Where are Cdks present and when are they activated?

Answer 9

present in all proliferating cells, only active once cyclins bind to them and after sequential phosphorylation (2x) by activating kinases & dephosphorylation (1x) by activating phosphatase

Question 10

What happens to the cyclin concentration within the cell during the cell cycle?

Answer 10

concentration fluctuates throughout, it is cyclic = produced & degraded, it reaches a peak during mitosis and rises steadily during interphase

cyclical activation

Question 11

What checkpoint exists during S phase and G2 phase?

Answer 11

damaged or incompletely replicated DNA

Question 12

What checkpoint exists during mitosis phase?

Answer 12

chromosome improperly attached to mitotic spindle

Question 13

How do protein cascades work in the cell cycle?

Answer 13

One kinase gets activated through phosphorylation and then activates another kinase by phosphorylation again and so forth

Question 14

What do kinase cascades in the cell cycle lead to?

Answer 14

signal amplification as one kinase can start a cascade w/ many more kinases, diversification as gives the options of different pathways,
opportunity for regulation

Question 15

What are the names of the Cdks?

Answer 15

Cdk1, Cdk2, Cdk4, Cdk6

Question 16

What are the names of cyclins?

Answer 16

Cyclin A, Cyclin B, Cyclin D, Cyclin E

Question 17

Why is sequential phosphorylation and dephosphorylation in activation of Cdks important in the cell cycle?

Answer 17

to avoid abhorrent cell cycling, it’s multiple steps each provide a step that can be regulated

Question 18

How does positive feedback drive the cell cycle forward?

Answer 18

example with M-Cdk:

active M-Cdk signals the activation of inactive phosphatase (needed to activate more M-Cdk by dephosphorylation) and signal for Cdk-inhibitory kinase which is needed in phosphorylation of the inactive M-Cdk too.

= explosive increase in M-Cdk to drive the cell rapidly from G2 to M phase

Question 19

What inactivates (turns off) cyclins?

Answer 19

Ubiqutination (cellular post it notes)
= placing a marker onto the cyclin that signals for its destruction

-> cyclin then gets destroyed

Question 20

Why do Cdks become sequentially active?

Answer 20

stimulate synthesis of specific genes that are required for the next phase = direction & timing to the cycle

Question 21

What is retinoblastoma protein (Rb) & what is its mechanism?

Answer 21

tumour supressor, “molecular brake”

found in all nucleated cells

mechanism: active Rb binds to transcription factor and keeps it in the inactive form

Question 22

What happens when Rb is missing or inactive?

Answer 22

cell cycle progresses when it shouldn’t = tumour

eg. children’s eye tumour

Question 23

How do cells inhibit Rb if the cell is going to proliferate?

Answer 23

Cdks phosphorylate Rb, Rb->inactivated & activated TF is now free to act on target genes

Question 24

What are E2F family members?

Answer 24

transcription factors that regulate the expression of several genes needed for cell cycle progression (protooncogenes-incl c-myc, cell cycle - incl. cyclins & cdks, & DNA synthesis - incl. DNA polymerase, thymidine kinase)

Question 25

Which tumour supressor molecule detects damaged DNA in G1 phase and how?

Answer 25

p53

when DNA damaged, will activate protein kinases which phosphorylate p53 -> activated & stable p53 -> binds to regulatory site of p21 gene which undergoes transcription & translation

-> p21 family membranes -> cyclin: Cdk complex inhibited

Question 26

What happens to p53 in the absence of DNA damage?

Answer 26

degraded in proteasomes

Question 27

What is EGFR/HER2?

Answer 27

(epidermal growth factor receptor)

oncogene that is mutationally activated or overexpressed in breast cancers

Question 28

What is a treatment for HER2+ metastatic breast cancer?

Answer 28

Herceptin antibody that blocks HER2+ signaling

Question 29

What is Ras?

Answer 29

oncogene mutationally activated in many cancers

Question 30

What is Cyclin D1?

Answer 30

oncogene overexpressed in 50% breast cancers, cells cycle when shouldn’t be