Cell Replication Flashcards

1
Q

What is the cell cycle

A

Duplication
Division
Coordination

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2
Q

Which phases make interphase

A

G1

S (DNA replication)

G2

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3
Q

What is the M phase

A

Mitosis and cytokineses

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4
Q

What is the quiescent phase

A

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

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5
Q

Why might a cell pause during cell cycle

A

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

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6
Q

How might cells leave G0

A

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

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7
Q

G1

A

Cell growth
Contains checkpoint which checks for damaged dna

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8
Q

G2

A

Preparation for mitosis
Checks for damaged or incompletely replicated DNA

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9
Q

Ras/RAF/MEK/REK

A

Increase protein synthesis
Inhibit protein degradation
Allows net growth of cell

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10
Q

C-Myc

A

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

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11
Q

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

A

C-Myc
Increases concentration if cyclin D

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12
Q
  • What is the purpose of Cyclin dependent kinase (Cdk)?
A

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

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13
Q

Where are cdks found

A

In all proliferating cells

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14
Q

When are cdks active

A

Only when bound to cyclin

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15
Q

What allows progression into s phase

A

Cdk 4/6 binding to cyclin D

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16
Q

What effect does phosphorylation have on kinases

A

Activates them

17
Q

What effects does phosphatases have on kinases?

A

Turns them off

18
Q

How are cdks activated

A

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

19
Q

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

A

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

20
Q

How are cyclins turned off

A

Cyclin is ubiquitylated
Leads to destruction of cyclin
Cdk is inactive

21
Q

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

A

Cyclin D- Cdk4/6 Complex

22
Q

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

A

Cyclin E - Cdk2 Complex

23
Q

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

A

Cyclin A - Cdk2 Complex

24
Q

Which Cyclin-Cdk complex is formed after this?

A

Cyclin B - Cdk1 complex

25
Q

How are specific timing and direction given to cell cycle

A

Cdks become sequentially active and stimulate synthesis of genes

26
Q

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

A

Cyclins are susceptible to degradation so they can be formed again

27
Q

Cancers replication rate

A

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

28
Q

Retinoblastoma

A

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

29
Q

What does rb do in a resting cell

A

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

30
Q

What does mitogen signalling do to rb in a proliferating cell

A

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

31
Q

What is the function of p53

A

They arrest cells with damaged dna in G1

32
Q

P53

A

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

33
Q

What happens when dna damage is detected

A

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

34
Q

Oncogenes

A

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

35
Q

Tumor suppressors

A

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

36
Q

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

A

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