Cell Cycle Flashcards

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1
Q

What happens in the S phase?

A

This is where dna replicates, and so do the centrosomes (although they usually stay together)

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2
Q

What happens in prophase?

A

In prophase, we start to see DNA condensation, the kinetochore forms on the centromere (getting ready to capture microtubules)

  • -Centrosomes also separate to move to opposite poles
  • -Nuclear breakdown happens and chromosomes are released into the cytoplasm. The microtubules then invade the nuclear space and make attachments to the kinetochore to start to set up the spindle
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3
Q

What happens during metaphase?

A

During metaphase, the sister chromatids are at the metaphase plate, and are oriented so that each sister kinetochore/chrimatine are connected to only one pole

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4
Q

What happens in anaphase?

A

At the end of anaphase when chromosomes are close to the poles, we see a decondensation of the chromosomes. In animal cells, we can also see the building up of actin around what used to be the metaphase plate, starting around the cell membrane and contractions of the actin interacting with myosin to bring the division of the cell

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5
Q

What are the two phases that the M phases is divided into?

A

M phase is divided into 2 separate phases; nuclear division (mitosis) and cell division (cytokinesis)

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6
Q

What are the 3 phases in interphase?

A

G1, S and G2

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7
Q

What are the G/Gap phases for?

A

The G/Gap phase prepares for the next stage of the cell cycle and ensures it is ready for transition
-In G1, it makes proteins and enzymes required to get through S phases

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8
Q

What happens if G phases recognize that the cell is not suitable for transition?

A

If conditions/signals are not suitable for cell division, the cell may exit G1 and enter the G0 (zero) phase . Cells are not dividing or preparing to divide

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9
Q

What are the 3 major regulated transitions (checkpoints) of the cell cycle control system?

A
  1. Start Transition: the transition between G1 to S
    This is also for is the cell is damaged and may be stopped from entering synthesis
  2. G2/M Transition: cell going from G2 to mitosis: asking things like “is the DNA replicated?”
  3. Metaphase to Anaphase Transition: asking things like “are all chromosomes attached to the spindle”
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10
Q

what is the difference between Cdk proteins and cyclin proteins

A

Cdk protein levels are constant during the cell-cycle

Cyclin protein levels rise and fall during the cell-cycle by synthesis and degradation.

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11
Q

What are the four major classes of cyclins?

A
  • G1/S n as S cyclin, starts to come up. This will reach its peak as we move into S phase
  • S cyclin
  • M-Cyclin
  • The fourth type of cyclin is the G1 Cyclin (not all cells have it)
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12
Q

What are the four cyclins responsible for?

A
  1. G1/S-Cyclin: used to move through START
  2. S- Cyclin: used for transition into S phase
  3. M-Cyclin: helps cell transition into mitosis
  4. G1-cyclin levels rise gradually during G1 phase and fall during M phase. They help regulate activity of G1/S-Cdks
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13
Q

What are the roles of the 4 Cyclic-CDK complexes?

A
  1. G1-Cdk: Helps regulate G1/S cyclins
  2. G1/S-Cdk: commit cell to move though “start” and stimulate centriole duplication at start of S-phase (they first inactivate APC/C)
  3. S-Cdk: commit cell to go though S phase, by initiating DNA replication and histone synthesis. The duplication of centrioles are also continued by S-CDK
  4. : M-Cdk: involved in phosphorylating a number of substrates to help initiate early stages of mitosis (G2-M transition)
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14
Q

How is Cdk FULLY activated?

A

Cdk is partially activated when it binds to its cyclin. However, full activation of Cdk happens only when a Cdk-activating kinase (CAK) comes in and phosphorylates the Cdk’s T-loop, which changes it confirmation to improve binding to a substrate

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15
Q

What are two ways Cdk activity can be suppressed?

A

1) Wee1 Kinase - adds two phosphates to different parts of the CDK enzyme and inhibits the cyclin-CDK complex (can be removed by a Cdc25 phosphatase, in order to reactivate the cyclin-CDK complex)
2) Cdk inhibitor proteins (CKIs) - binds to the CDK cyclin complex which changes its active site’s conformation so that it can no longer bind its substrate (example of CKI is p27)

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16
Q

What are 4 Cdk regulators?

A

1) Cdk-activating kinase (CAK) -Phosphorylates CDK and fully activates them by phosphorylating the t-loop
2) Wee1 Kinase - Adds inhibitory phosphates, inhibiting CDK activity
3) Cdc25 phosphatase - Removes inhibitory phosphates to reactivate CDK
4) CKIs (CDK inhibitor protein) - Bind to cyclin-CDK complexes and inhibit their activity

17
Q

How is Met-Ana transition triggered?

A

Proteolysis: Although transition from start, through G2 to M, is mediated by phosphorylation, the transition from metaphase to anaphase is mediated by protein destruction.
APC/C acts on proteins and adds ubiquitous to the proteins; this targets the proteins to proteasome, which are for destruction

18
Q

Helicase is used to unwrap two dna strands. What complex activates Helicase?

A

In eukaryotic cells, DNA replication is initiated at the origin of replication. The activity of S-CDK complex that phosphorylates proteins which activate the Helicase to unwrap the two DNA strands

19
Q

What are some of the early mitotic events that M-Cdk is responsible for?

A
  • chromosome condensation
  • nuclear envelope breakdown
  • separation of centrosomes and setting up mitotic spindle
20
Q

How does M-Cdk make the cell lose its nuclear envelope at. the end of prophase?

A
  • M-CDK will start to phosphorylate nuclear pore complex subunits, which will change their confirmation so that they no longer interact with proteins which leads to disassembly
  • They also phosphorylating the nuclear lamins which will make them disassemble and ultimately results in the loss of the nuclear envelope
21
Q

Does M-Cdk go into anaphase?

A

No, M-Cdk regulates mitosis up to metaphase and helps activate APC/C by helping it interact with Cdc20.
- Anaphase-promoting complex (APC/C) is what. triggers anaphase.

22
Q

How is APC/C involved in separating the sister chromatids?

A

The M-Cdk complex will help APC/C interact with a protein called Cdc20, which will make APC/C activated. When APC/C is active, it will act on securin so that securin is polyubiquitinated which will break it down. This frees up seprase and changes it confirmation to be active
- Seprase then is able to break down cohesins and lead to the separation of sister chromatids

23
Q

How does cytokinesis happens?

A

In the area where the metaphase plate used to be, a contractile ring (actin-myosin) is formed, which is what pinches the cell into 2. Rho-GEF will attacth GTP to RhoA to activate it, which in turn, will activate formin which will stimulate the polymerization of actin in the area where the ring will form
-RhoA will also act on Rho-activating kinases; the mysoins from this will assemble at the area of the contractile ring and becomes active

24
Q

How does the cell escape from G1 where there is low Cdk activity?

A

An external signal is needed for cells to escape G1 and get into the cell cycle again
In multicellular organism, an external signal called mitogen is used, which typically come from being secreted by other cells

25
Q

What are 3 Controlling factors of Cell Division and Cell growth

A
Cell division (mitogens stimulate cell division) 
Cell growth (growth factors stimulate increase in mass) 
Cell survival (survival factors – suppress cell suicide/apoptosis)
26
Q

What are PDGF and EGF?

A

PDGF: Platelet derived growth factor (RTK Receptor)
EGF: Epidermal growth factor (RTK receptor)
These two molecules are part of the mitogen pathway and can act as both growth factors and mitogen

27
Q

What is the mitogen pathway?

A

The mitogen with the mitogen receptor will activate Ras which will lead to the activation of MAP-Kinase. The kinase activity will lead to the activation of transcription regulatory proteins which will affect gene expression.
-One of the major genes that if often activated in the mitogen pathway is Myc

28
Q

How does Myc contribute to cell growth and division?

A

Myc is a gene regulatory protein that turns on the gene for G1-cyclin
Once G1/cyclin starts to be transcribed, it can form active G1-CDK complexes. The active G1-CDK complex will lead to the transcription of other genes that are involved in cell growth and division

29
Q

How does the activation of G1-Cdk lead to transcription of G1/S-Cyclin?

A

A substrate of G1-Cdk phosphorylates RB, changing RB’s confirmation so that it releases a regulatory protein called E2F. Once E2F is released, it will initiate the transcription of G1/S Cyclins
-this means that Rb acts as a regulator that will prevent movement throughout the cell cycle

30
Q

What are checkpoints in the cell cycle control system?

A

Checkpoints at each major transition monitor for problems.

Typically, these checkpoints are where inhibitory mechanisms act on cyclin complexes - these problems delay transitions

31
Q

What are some checkpoints in the cell cycle?

A

DNA damage can stop the cell cycle in G1 by inhibiting activity of G1/S and S-CDK
Unreplicated DNA and DNA damage can prevent transition from G2 to M phase

32
Q

How does DNA damage lead to transcription of p21?

A

Normally, p53 will be broken down by Mdm2 Ligase. In damaged DNA, p53 will become phosphorylated and activated, which will release from Mdm2 and ultimately lead to production of p21.
-p21 is a CKI, which is a cdk inhibitor protein for G1/S and S Cdlks

33
Q

How is p53 related to human cancer?

A

The normal function of p53 is to inactivate cyclin-CDK complexes
This is a from of a tumor-suppressor gene
If p53 activity fails due to a mutation, it means that damages DNA is going to be replicated and you may end up with daughter cells that have more mutations than normal