13.1 Cell Cycle Control II Flashcards

1
Q

How does negative feedback result in oscillations of protein activity?

A

A Kinase protein will phosphorylate itself as well as other copies of itself in a course downstream targets. This phosphorylation makes individual proteins more active.

Once the proteins have been activated they phosphorylate all other copies of the protein more rapidly. (you see a sharp rise in the activity of the kinase.

This will slowly begin to activate its inhibitor until it reaches a point where there is more active inhibitor than active kinase.

Kinase falls rapidly and since it is no longer activating the inhibitor, the inhibitor also slowly falls as its phosphates are hydrolyzed.

once the inhibitor activity has fallen to some base level the process repeats

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2
Q

How is expression of cyclins and APC in the G1 phase?

A

expression of m and s cyclin is low and APC activity which began in meta/anaphase transition is high.

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3
Q

Why is expression of cyclin low in G1 phase?

A

1) Cyclins is low b/c transcription factors regulating the expression of these cyclins are inhibited
2) Active APC is targeting S and M phase cyclins for degradation but not G1/S cyclins
3) there is a high level of active CDK inhibitor that is important for keeping CDK activity down even if a small amount of the cyclins get expressed.

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4
Q

What activity is not present in G1 phase?

A

NO CDK activity in G1 phase and there is no S or M phase cyclin activity. APC does not inhibit G1/S CDK so this is active in G1

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5
Q

How is G1/S of cell cycle initiated?

A

by control of signaling systems which are regulated by the binding factors called mitogens to the cell surface receptors.

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6
Q

What are mitogens?

A

Mitogens are factors that drives cell into the cell cycle

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7
Q

Which cyclins are present in G1/S phase? Which one becomes functionally active in G1/S?

A

G1/S cyclin and S Cyclin are expressed S is not expressed till mid G1.

Initially, the activity of APC is still active and it is still targeting S-cyclin for degradation and the inhibitors of S and M phase cyclins are still around so the only CDK that becomes functionally activated is G1/S CDK.

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8
Q

In G1/S phase what is anaphase promoting complex doing? is it active or inactive?

A

Active in the beginning but then when G1/S CDK becomes functionally activated it will inactivate the APC complex and also targets the CDK inhibitors for degradation

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9
Q

What turns off all the inhibitors that are keeping the cell in G1?

A

The activity of G1/S CDK

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10
Q

What results from the activity of G1/S-Cdk?

A

activity of all inhibitors turn off and all S-CDK levels start to go up

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11
Q

What leads to the suppression of gene expression of G1/S cyclin?

A

G1/S-CDK activates proteins that degrade G1/S cyclins and that ends up suppressing gene expression of G1/S cyclin as the cell goes into S phase.

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12
Q

What drives the cel into S phase?

A

The rise of S-CDK activity drives the cell into S phase

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13
Q

In S phase how are the levels of G1/S cyclin? What about APC?

A

G1/S cyclin levels go down and APC is low b/c it was turned off and there is nothing to turn it back on.

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14
Q

What is the SFC complex ?

A

SFC complex targets a CDK inhibitor for degradation, which is important for keeping cells in G1.

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15
Q

What allows the cell to move forward into the S phase?

A

Destruction of the CDK inhibitor by SFC allows the cell to move forward into S phase

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16
Q

Why do levels of M cyclins rise in the S phase?

A

M cyclin genes are no longer repressed so the expression of M cyclin rises b/c APC is inactive.

17
Q

How is M-CDK kept in an inactive state in G2 phase?

A

During G2, M-CDK is kept in an inactive state by the activity of CKI proteins

18
Q

What happens when M-CDK levels get high enough in early M phase?

A

there is a sudden dramatic activation of M-CDK through the function of two feedback loops. The sudden rise drives the cell into motion

1) one loop inactivates the inhibitor of -CDK
2) The other loop activates an activator of M-CDK

19
Q

What happens when cdc20 is phosphorylated by M-CD?

A

cdc20 will bind to APC complex and activate it. And in turn APC complex will target M-cyclin for degradation.

(this is another example of the feedback loop system)

20
Q

In the M cycle, what does APC inhibit? What does it activate?

A

G1/S, S, and M cyclin expression are inhibited and S and M are targeted for destruction.

Activates: inhibitors of M-CDK and S-CDK

21
Q

What happens when M-CDK activity declines?

A

APC activity will also decline rapidly and this will then allow build up of S and M cdk to begin again.

22
Q

How can cells prolong the G1 phase?

A

by use of an alternative activator of APC called CDh1 and the use of an M-Cdk so its activity rises only when M-cyclin levels fall at the end of mitosis.

23
Q

Where is DNA replication started on chromosomes? is it at random?

A

DNA replication is not started randomly on chromosomes. it is initiated at a unique location called origins of replication.

24
Q

What initiates the process of DNA replication in S phase?

A

before DNA synthesis actually starts by the formation of complexes called pre-replication complexes at origins of replication.

25
Q

how are pre-replication complexes formed?

A

formation of these complexes requires access to the origins of replication and the presence of active APC (this can only happen at the end of mitosis and in early G1).

When cells enter S phase, M phase CDK begins to be activated and the pre-replication complexes recruits a different complex to the origins of replication called the pre-initiation complex. Pre-replication complex is dismantled during this step. This preps the site for the initiation of DNA replication

26
Q

What is the only way that the pre-initiation complex can be formed?

A

the pre-initiation complex can only form where there is a pre-replication complex and these are only created at the end of mitosis.

27
Q

When will DNA that is created by replication get set up for replication again?

A

at the end of mitosis

28
Q

Which proteins are found at the pre-replication site?

A

cell division proteins Cdc6 and Cdt1

29
Q

What do CDC6 and CDT1 do?

A

cell division proteins that bind to the origin of replication complex and facilitate the addition of six McM proteins.

30
Q

What are the 6 McM proteins?

A

McM proteins form a hexamer that is an active helicase (meaning it uses ATP to unwind DNA).

The addition of McM proteins creates a functional pre-replication complex and the origin is said to be licenses for DNA replication. With the preinitiation site it creates the active replication fork which recruits DNA polymerase and makes copies of DNA

31
Q

Together, what do the pre-initiation complex and McM helicase form?

A

they form an active replication form, which will recruit DNA polymerases and make copies of the existing DNA strands in S phase.

32
Q

In the S phase, DNA must be replicated only once, what prevents the formation of another pre replication complex until the end of mitosis?

A

S phase CDK phosphorylates cdc6 and the origin of replication complex and this releases cdt1 from the origin of replication. cdc6 is then degraded by proteases and this prevents the formation of another pre replication.