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Biol 2520 > Lecture 18 -cell Cycle > Flashcards

Lecture 18 -cell Cycle Flashcards

1
Q

What is a cell cycle

A

A series of events that need to tAke place for the cell to divide and its content to duplicate

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2
Q

How many phases are in the eukaryotic cell?

A

4

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3
Q

What are the phases of cell didvisionnin euk cells?

A

G1
S -DNA replicates
G2
M- mitosis + cytokinesis

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4
Q

Which phase takes the longest and how much

A

Interphase take 90% of time

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5
Q

Cells that are stuck at the end of G1 phase are called…

A

Cells in G0 state ( arrest stage)

Quiescent

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6
Q

What are the 3 cell cycle groups

A

1- cells that enter a permanent G1 phase (Arrest stage )
Once differentiated Remain in this stage untill they die
2- cells that don’t divide normally but can be induced
3- cells that divide regularly

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7
Q

Most cells fall in which type of category?

A

Mostly cells are in G0 state but most of them can re enter the cell cycle when it needs to divide

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8
Q

What determines how much time the whole cell cycle will take

A

The amt of time taken by the interphase

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9
Q

Whats the main thing happening in G1 phase?

A

Cell grows and carries out normal metabolism

Organelles duplicate

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10
Q

S ( synthesis)

A

DNA and chromosome duplication

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11
Q

What happens in G2 phase?

A

Cell grows and prepares for mitosis

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12
Q

What happens in M phase?

A

Mitosis/ karyokinesis

Cytokines

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13
Q

What is required to move on to the next stage

A

Cell signalling

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14
Q

What signals the cells in Go to divide , what initiates the cell cycle?

A

Ras signalling of MAP kinase cascade triggered by RTK receptor

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15
Q

How does the RTK triggers or speeds cell division

A

1- MAP kinase cascade triggered by RTK
2- cells produce Epidermal growth factor
2- this trigger stem cells and other cells
4- this signalling pathway turn on the transcription of specific genes , Eg cyclins , this speeds up cell division

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16
Q

Cell cycle control system is similar in euk

A

True

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17
Q

CELL CYCLE CONTROL SYSTEM

————- is like the black box in the cell

A

Cell cycle control.

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18
Q

What are the major components of the cell cycle control system?

A

1- cyclins

2- cyclin dependent protein kinases ( cdks)

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19
Q

How does the cell cycle control system work ?

A

The cell control cycle has brakes or checkpoint to arrest the cell cycle
If a stage is incomplete, the process will come to a stop
Eg- if DNA is damaged , the cell cycle comes to a stop, the DNA is repaired before proceeding

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20
Q

Overall Purpose of the cell cycle control system ?

A

Ensures that the key processes in the cycle occur in the proper sequence

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21
Q

Maturation promoting factor is a complex of

A

Cdk 1 + cyclin B

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22
Q

Role of cyclin in maturation promoting factor- MPF /M cdk ( cyclin B + cdk)

A
  • regulates cdk activity
  • levels rise and falls throughout
  • helps direct the cdk to the target proteins that the cdk phosphorylates
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23
Q

Role of cdk in maturation promoting factor

A
  • a kinase protein that adds a phosphate from ATP to other proteins , to modify target protein
24
Q

How does Progress to the M phase occur?

A

-Cdk+ cyclin = enzymatically active (M cdk)
-cdk is phosphorylated at 2 adj sites by inhibitory kinase wee1
-wee1 keeps it inactive until cdc25 phosphatase removes the phosphate
The complex the:-
- The cyclin also helps direct the cdk to the target proteins that the cdk phosphorylates
- cyclin helps cdk enzymic activity

25
Q

Level of cyclin during and btw stages

A

Entering mitosis - increasing towards the highest point
Mitosis- highest point
Leaving mitosis- steep fall and 0 before leaving
Entering interphase - 0
Interphase - 0 right in beg , then gradually increasing
Leaving interphase - gradually to increase

26
Q

What regulates the activity of cdks

A

Accumulation of cyclin

27
Q

Formation of cyclin - cdk complex drives entry to what stages

A

S phase and M phase

28
Q

What helps in the formation of active M cyclin - cdk complexes

A

Increasing concentration of relevant cyclin called - M cyclin ( cyclin B)

29
Q

What happens when enough MPF is triggered ?

A

It triggers mitosis
- prepares chromosome for degradation by phosphorylates H1 histones - causes DNA to condense
- activates micro tubules proteins to assemble the mitotic spindles
- shutdown Wee1 and promote production of mcdk - when an mcdk is activated it phosphorylates more cdc25 which then removes phosphate from mcdk , activating it
POSITIVE FEEDBACK LOOP

30
Q

Overall what determines if the cell cycle will transition from one phase to another

A

Cyclin / cyclin Cdk complex
Eg Mcdk
G1/ Scdk
Scdk

31
Q

What drives entry to S phase through G1 phase

A

Active G1/S cdk phosphorylates regulatory proteins that activate transcription of genes required for DNA replication

32
Q

What drives entry to M phase

A

When the M cdk complex is active , the cdk can phosphorylate a different set of regulatory proteins

33
Q

How is cyclin concentration regulated?

Hint- how is the amount of any protein regulated

A

Regulated by ubiquitin medated degradation

Uniquitin tags S or M cyclin for degradation in proteosome

34
Q

As said earlier whta regulates cdk activity

A

Cyclin

Eg cyclin degradation inactivates cdk

35
Q

What regulates cyclin - cdk

A

Kinases and phosphatase regulate activation and inactivation
And cyclin regulates formation

36
Q

How is M cdk activated?

A
  • once the M cyclin cdk is active
  • it is phosphorylated at 2 adj sites by an inhibitory protein kinase called wee1
  • this this keeos the M cyclin cdk inactive untill
  • phosphatase Cdc25 removes these phosphates
37
Q

Wee 1 is part of checkpoint , what does it check ?

A

Checks if cell is big enough for mitosis

38
Q

Activity of cdk can be blocked by 2 methods , state them ?

A
  • phosphorylation by inhibitory kinase wee1( discussed earlier)
  • also be blocked by cdk inhibitors (p27)
39
Q

How do cdk inhibit cdk activity⁉️⁉️

A
  • Cdk inhibitory protein (p27) binds to an active cyclin cdk complex
  • attachment prevents the cdk from phosphorylating target proteins required for progress through G1 inti S phase
40
Q

Jist like wee1, cdk inhibitors are also part of checkPoint . What do they check

A

Check if envr conditions are favourable

Also gives more time for cells to grow

41
Q

What happens DNA replication not complete or DNA damage during S or G2 phase

A

cdc25 removed phosphate from M cdk ( activating it) ,allowing it to progress through mitosis. When DNA is damaged , Inhibition of activating phosphatase Cdc25 , Blocks entry to mitosis- part of G2 checkpoint

42
Q

What happens if Chromosomes not attached to spindles

A

Inhibition of APC/C activation delays exit from mitosis

43
Q

What happens if Environment not favourable in
G1
G2

A 
Cdk inhitors (p21) inhibit S- cdk , block entry to S phase 
Cdc25 inhibited, preventing activation of mcdk
44
Q

What promotes the production of cyclin that stimulate cell division

A

Mitogens
Mitogens turn on cyclin genes by activating cell signalling pathways
Absence of mitogens causes the cell to arrest in G1 or G0

45
Q

What promotes cell proliferation and how ?

A

Mitogens , by inhibiting the Rb protein

  • In the absence of mitogens, de phosphorylated RB proteins holds specific transcription regulators in an inactive state
  • Mitogens binds to the cell surface receptors activate intracellular signalling pathways that lead to the formation and activation of G1- cdk and G1/ s - cdk complexes
  • these complexes phosphorylate and thereby inactivate , the Rb protein , releasing the transcription regulators needed to activate the transcription of genes / cyclins required for entry in S phase
46
Q

Which transition itself is a critical checkpoint

A

G1 -> S phase

47
Q

What is like a 4 way stop ?

A

G1 to s phase

48
Q

What are the things that can happen in the g1 to s transition

A

1- cell can commit to completing another cycle
2- cells can withdraw temporarily until conditions are right
3- withdraw from cell cycle and enter g0 , either temp or permanently in case of terminally differentiated cells

49
Q

Then what exactly decides what to do out of these 3

A

Intracellular and extracellular signals decide if the cell proceeds to S phase or G0 phase

50
Q

We saw that s cdk and m cdk is 0 at G1 phase , how does this happen

A

S cdk and M cdk are inactive in G1

  • by eliminating all existing cyclins
  • block the synthesis of new cyclins
  • recruit cdk inhibitor proteins
51
Q

What happens if DNA is damaged in G1

A

DNA damage can arrest cell cycle in late G1 ( G0 arrest phase)

  • kinase work by
    activating Tp53 and
    haling its rapid degradation
  • activated p53 accumulates and stimulates the transcription of the gene that encodes the cdk inhibitor protein p21
    P21 binds to G1/ S- cdk and S-cdk and inactivates them , so the cell cycle arrests in G1
52
Q

3 ways cell enter non dividing stages

A

1- cells can delay progression through cell cycle until conditions become favourable or until DNA damage is fixed
2- cells can also withdraw from cell cycle permanently ( terminally differentiated cells)
- cyclin and cdk genes permanently shut down
- eg muscle cells, nerve cells
3- cells can withdraw from cell cycles temporarily
- enter into G0 until stimulated to proliferate

53
Q

Cell division rate depends on

A

The time soent in g0 and G 1 phase

54
Q

Role of S cdk in S phase

A
  • initiates DNA replication and blocks re replication

Activates helicase and recruits other proteins like (Cdc6) to the replication fork

55
Q

Cyclin concentration is regulated by

A

Ubiquity medial degradation
Or
Transcription genes activated by mitogens or RAS signalling

Biol 2520 (16 decks)

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