Cell Cycle Checkpoints Flashcards

1
Q

Coordination between different events of the cell cycle is achieved by …

A

A system of checkpoints

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2
Q

Function of cell-cycle checkpoints

A

Prevents entry into the next phase of cell cycle until the events of the preceding phase have been completed

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3
Q

What are the 3 main checkpoints in the cell cycle?

A
G1 checkpoint (G1-S)
G2 checkpoint (G2-M)
M-phase checkpoint (metaphase-anaphase)
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4
Q

G1 checkpoint

A

Monitors the environment before allowing the cell cycle to progress

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5
Q

G2 checkpoint

A

Monitors the DNA for proper replication & the environment

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6
Q

M-phase checkpoint

A

Spindle assembly checkpoint (SAC)

Monitors that chromosomes for proper attachment to MTs & for proper alignment at the metaphase plate

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7
Q

What is needed for a cell to grow?

A

Growth factors

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8
Q

Growth factor, GEF, activates which pathway?

A

Ras pathway

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9
Q

How is Ras pathway involved in cell growth?

A

Activated Erk from the Ras pathway targets Cdk4/6

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10
Q

What is the ‘restriction point’ in cell growth?

A

The point at which cells are committed to entering the S phase and no longer need growth factors

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11
Q

Before restriction point …

A

growth factors needed

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12
Q

After restriction point …

A

growth factors not needed as cell is committed to S phase

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13
Q

What is the role of E2F in cell growth?

A

E2F is a transcription factor in the nucleus that transcribes the genes needed for cells to commit to S phase

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14
Q

What is the role of Rb in cell growth?

A

A protein that binds to E2F and inhibits it from transcribing genes needed for S phase

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15
Q

What is the role of Cdk4/6 in cell growth?

A

Once activated by Erk, they phosphorylate Rb which causes it to unbind from E2F

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16
Q

What is the effect of E2F not being blocked in cell growth?

A

Key S phase protein are expressed and the restriction point reached

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17
Q

What happens if the cell does not commit to S phase?

A

It enters a specialised state - G0 state

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18
Q

What is G0 state?

A

Cells can enter a non-dividing state in which they can remain in for a long period of time until signalled to emerge

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19
Q

What is the effect of DNA damage on the cell cycle?

A

DNA damage can arrest the cell cycle in G1 phase

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20
Q

What effect does inducing p21 have on the cell cycle?

A

p21 binds to and inhibits complexes of cyclin-cdk. In G1, this prevents phosphorylation of Rb so the cell remains in G1

Generally, it can bind to main cellular Cdks and block cell cycle at multiple stages

21
Q

What effect does inducing Puma have on the cell cycle?

A

Puma inhibits Bcl2, a key protein that inhibits cell death. So, inducing Puma will allow cell death to happen

22
Q

What is the role of p53 in cancer?

A

p53 is inactivated therefore cell cycle arrest and apoptosis are inhibited so unrestrained replication of damaged DNA leads to high rate of mutations that tend to become cancerous

23
Q

How does DNA damage prevent cells from entering M phase?

A

DNA damage activates ATR which activates Chk1 which phosphorylates and inactivates Cdc25 therefore cyclin B-Cdk1 is not activated

24
Q

What are mitogens?

A

Signals that stimulate cells to divide

25
Q

What is the effect of activating ATM and ATR on the cell cycle?

A

They activate and phosphorylate downstream kinases Chk1 and Chk2

26
Q

What is the effect of activated Chk1 and Chk2 on the cell cycle?

A

They phosphorylate and stabilise p53

27
Q

What is the effect of activated p53 on the cell cycle?

A

It induces two proteins: p21 and Puma

28
Q

What is the role of MCM and Cdt1 on replication?

A

These proteins help form the pre-replication complex

29
Q

If there is no DNA damage, what happens to p53?

A

it is degraded by associating with Mdm2

30
Q

What targets DNA for degradation?

A

Ubiquitin

31
Q

What are pre-replication complexes?

A

Pre-replication complexes sit on the DNA (just like E2F) but are are being inhibited from carrying out their role (replicating DNA) by Cdt1

32
Q

What is the effect of Ctd1 on pre-replication complexes?

A

Ctd1 is needed for the formation of pre-replication complexes, however, when Ctd1 is bound to the complexes they are silent and cannot start replicating

33
Q

What is the role of Geminin in S phase?

A

Geminin binds to Ctd1 and removes it from pre-replication complex so that replication can start

34
Q

What happens to Geminin in anaphase?

A

It is degraded therefore allowing Ctd1 to form pre-replication complex

35
Q

What is the ultimate goal of Geminin and Ctd1?

A

To ensure that the DNA replicates ONCE per cell cycle

36
Q

What complex is needed for the cell to enter anaphase?

A

APC/C (anaphase promoting complex/cyclosome)

37
Q

How is APC/C activated?

A

APC/C is activated when it associates with Cdc20 and they form a ubiquitin ligase

38
Q

What is the role of ubiquitin ligase?

A

It adds a protein of 76 amino acids called ubiquitin to proteins and targets them for proteolysis (degradation)

39
Q

What are the 2 targets of active APC/C?

A

Cyclin B and Securin

40
Q

What is the effect of active APC/C on cyclin B?

A

Leads to degradation of cyclin B so M-phase Cdk is no longer active

41
Q

What is the effect of active APC/C on securin?

A

Seperase binds to degrades cohesion proteins so that sister chromatids can be seperated

Securin keeps seperase in its inactive form

42
Q

What does Mad1 do?

A

Mad1 is attached to kinetochore and can change the conformation of Mad2 from open to closed when they bind

43
Q

What does Mad2 do?

A

When it is in a closed form, it binds to and inhibits Cdc20

44
Q

When there are no Mts attached to kinetochore:

A

cMad2 binds and inhibits Cdc20 so that cell doesn’t proceed to anaphase (because there are no Mts)

45
Q

When Mts are attached in a stable way to kinetochore:

A

Mad1 dissociates from kinetochore and stops producing closed form of Mad2

p31comet displaces cMad2 from Cdc20

Free Cdc20 can now associate with APC/C and activates it to initiate anaphase

46
Q

What does “Mts bound stably mean”?

A

Mts bound to kinetochore in amphitelic fashion (both kinetochores are attached to Mts from the two spindle poles)

47
Q

What are the 3 unstable forms of attachment?

A

Merotelic (only 1 kinetochore is attached to Mts that come from both spindle poles)

Monotelic (only 1 kinetochore is attached to MTs that comes from 1 spindle pole)

Syntelic (both kinetochores attached to Mts that come from 1 spindle pole)

48
Q

How does cell know that Mts are attached in stable manner?

A

When they are attached in amphitelic way, there is TENSION in chromatids and the amphitelic attachments move the kinetochore further away from Aurora B, preventing phosphorylation of key kinotchore proteins (this does not happen with 3 other attachments)

49
Q

What happens when 3 other attachments take place?

A

No tension, so aurora B phosphorylation of kinetochore proteins occurs - Ndc80 complex active which loosens MT attachments and allows them to reform correctly again