Cell Replication

Question 1

What is the cell cycle

Answer 1

Duplication
Division
Coordination

Question 2

Which phases make interphase

Answer 2

G1

S (DNA replication)

G2

Question 3

What is the M phase

Answer 3

Mitosis and cytokineses

Question 4

What is the quiescent phase

Answer 4

Inactive stage that occurs when cell leaves the cell cycle in absence of stimulus
Cell is non dividing not dormant
G0 is thus phase
Eg neurons skeletal muscles hepatocytes

Question 5

Why might a cell pause during cell cycle

Answer 5

DNA repair
Undergo apoptosis if mistakes in DNA replication are too much to repair

Question 6

How might cells leave G0

Answer 6

Response to extracellular factors eg growth factors
Signal amplification
Signal integration by other pathways
MAP kinases eg ras/raf/MEM/ERK

Question 7

G1

Answer 7

Cell growth
Contains checkpoint which checks for damaged dna

Question 8

G2

Answer 8

Preparation for mitosis
Checks for damaged or incompletely replicated DNA

Question 9

Ras/RAF/MEK/REK

Answer 9

Increase protein synthesis
Inhibit protein degradation
Allows net growth of cell

Question 10

C-Myc

Answer 10

Regulates cell cycle entry
Is an oncogene which is overexpressed in many tumors
C-Myc-transcription factor stimulates expression of cell cycle genes
Promotes G0 to G1

Question 11

What oncogene causes progression of cell from G0 to G1 phase and how does it do this?

Answer 11

C-Myc
Increases concentration if cyclin D

Question 12

• What is the purpose of Cyclin dependent kinase (Cdk)?

Answer 12

Phosphorylation and dephosphorylation of serine/threonine/tyrosine
Part of signallung events

Question 13

Where are cdks found

Answer 13

In all proliferating cells

Question 14

When are cdks active

Answer 14

Only when bound to cyclin

Question 15

What allows progression into s phase

Answer 15

Cdk 4/6 binding to cyclin D

Question 16

What effect does phosphorylation have on kinases

Answer 16

Activates them

Question 17

What effects does phosphatases have on kinases?

Answer 17

Turns them off

Question 18

How are cdks activated

Answer 18

Cyclin is produced and binds to cdk

Phosphorylation of Cdk-cyclin complex at inhibitory and activating sites of Cdk

Dephosphorylation by phosphatase which removes inhibitory phosphate from Cdk, activating it

Question 19

How does positive feedback work to increase the amount of active Cdk?

Answer 19

The activated Cdk activates more of the phosphatase to remove further inhibitory phosphates from Cdk-cyclin complexes

Question 20

How are cyclins turned off

Answer 20

Cyclin is ubiquitylated
Leads to destruction of cyclin
Cdk is inactive

Question 21

Which Cyclin-Cdk complex leads to the progression into G1 phase

Answer 21

Cyclin D- Cdk4/6 Complex

Question 22

Which Cyclin-Cdk complex leads to the progression into S phase

Answer 22

Cyclin E - Cdk2 Complex

Question 23

Which Cyclin-Cdk complex leads to the progression into M phase?

Answer 23

Cyclin A - Cdk2 Complex

Question 24

Which Cyclin-Cdk complex is formed after this?

Answer 24

Cyclin B - Cdk1 complex

Question 25

How are specific timing and direction given to cell cycle

Answer 25

Cdks become sequentially active and stimulate synthesis of genes

Question 26

How does the activity of cyclins allow the cell cycle to be cyclical

Answer 26

Cyclins are susceptible to degradation so they can be formed again

Question 27

Cancers replication rate

Answer 27

Embryonic cells have a faster rate of replication Tumor cells-excessivedysregulated cell replication

Question 28

Retinoblastoma

Answer 28

Eye tumor suppressor If rb protein missing or inactive there are issues with cell cycle progression Rb acts as a brake in cell proliferation

Question 29

What does rb do in a resting cell

Answer 29

Rb sequesters a transcription factor in an inactive form commonly E2F family The TF can’t turn on genes needed for cell cycle progression eg dna polymerase and thymidine kinase

Question 30

What does mitogen signalling do to rb in a proliferating cell

Answer 30

Activation of intracellular signalling through mitogens leads to production of G1-Cdk and G1/S-Cdk complexes They **phosphorylate the active Rb** that is **bound to TF**, **inactivating it** which **releases the TF** Target genes like **DNA polymerase** and **thymidine kinase** can now activate

Question 31

What is the function of p53

Answer 31

They arrest cells with damaged dna in G1

Question 32

P53

Answer 32

Recognizes double stranded breaks and activates kinases that phosphorylate p53 In absence of dna damage it is degraded

Question 33

What happens when dna damage is detected

Answer 33

If dna damage is detected active p53 gene binds to regulatory region on p21 gene Transcription of p21 and dna occur P21 family members are inhibitors of cyclin/Cdk complexes Loss of function mutation in over 50% of humans

Question 34

Oncogenes

Answer 34

Ras-mutationally activated in cancers Cyclin d1 over expressed in 50% of breast cancers C-Myc overexpressed in many tumors EGFR/HER2 mutationaly activated or over expressed in cancers

Question 35

Tumor suppressors

Answer 35

Rb loss of function mutations in 80% of small cell lung cancers P53 loss of function mutations in over 50% of cancers

Question 36

How might over expression of c myc lead to aberrant cell cycling and cancer

Answer 36

Induces expression of cyclin D which drives inappropriate entry into G1-S phase