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BMS > Cell Cycle Control > Flashcards

Cell Cycle Control Flashcards

1
Q

Can be the basis of many different medical disorders including autism, cataracts, and other congenital disorders, but the most significant is cancer

A

Deregulated cell growth

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2
Q

The basis of cancer

A

Deregulated cell growth

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3
Q

Accounts for nearly one quarter of the deaths in the US, and is exceeded only by heart diseases

A

Cancer

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4
Q

Will be the most frequently diagnosed cancers

in men and women, respectively, followed by lung and colorectal cancers both in men and in women.

A

Prostate and Breast cancer

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5
Q

Complex network of regulatory proteins that governs
DNA replication and segregation of chromosomes
through an ordered series of biochemical switches

A

Cell cycle control system

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6
Q

The cell cycle is a network of

A

Positive and negative feedback loops

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7
Q

The cell cycle MUST occur in a particular

A

Order

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8
Q

The cell cycle is controlled by a series of

-Serve as the point of no return

A

Biochemical switches

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9
Q

Once the biochemical switch is on, the cell must proceed to the

A

Next point

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10
Q

What are the two types of controls that regulate the cell cycle?

A

Internal and external

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11
Q

Monitors progression through the cell cycle so that each step happens in succession and delays later events until previous ones re completed

A

Internal cell cycle control

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12
Q

Cells respond to environmental signals in order to stimulate cell division when more cells are needed and to block cell division when no cells are needed

A

External cell cycle control

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13
Q

Function within the cell to ensure the correct progression of cell cycle events

A

Internal controls

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14
Q

Allow cells to respond to both positive and negative environmental cues

A

External controls

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15
Q

Defines the process where a cell duplicates itself and divides to make 2 daughter cells

-passes on IDENTICAL genetic information to daughter cells

A

Cell cycle

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16
Q

The cell duplicates itself during

A

S phase

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17
Q

The cell produces the two daughter cells during

A

M phase

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18
Q

M phase is separated in to which 2 stages?

A
  1. ) Mitosis

2. ) Cytokinesis

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19
Q

Nuclear division of the cell

-goes from prophase to telophase

A

Mitosis

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20
Q

Cytoplasmic division into two daughter cells

-the last part of telophase

A

Cytokinesis

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21
Q

Interphase is all of the cell cycle that is not the M phase, and is made up of

A

G1, S, and G2 phases

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22
Q

Time delay for cell to grow (accumulate mass) and monitor intra- and extra- conditions

A

G1 and G2 phases

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23
Q

A point that exists at the end of G1 that measures the favorability of the environment

A

Restriction point

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24
Q

Once cells pass through the restriction point, they are committed to

A

DNA replication

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25
Q

If the environmental signals become unfavorable AFTER the restriction point is passed, can the cell stop DNA replication?

A

No

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26
Q

What happens if the environmental conditions are unfavorable at the restriction point?

A

Cells are arrested in G0 until conditions become favorable

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27
Q

Allows the cell cycle to keep progressing forward and initiate the cellular events required for each step of the cell cycle

A

Regulated production/activation of proteins at specific times

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28
Q

Triggers mitosis machinery

A

Assembly of mitotic spindle

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29
Q

Cell cycle progression is controlled by the sequential activation of a set of kinases called

A

Cyclin dependent kinases (Cdks)

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30
Q

Phosphorylate different proteins at different times in the cell cycle, which then initiates or regulates key events in the cell cycle

A

Cyclin-dependent kinases (Cdks)

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31
Q

For activity, Cdks are dependent on other proteins called

A

Cyclins

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32
Q

The activity of these kinases increase or decrease during different phases of the cell cycle

A

Cdks

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33
Q

Different cyclins exist for different phases of the

A

Cell cycle

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34
Q

Cyclins bind to their partner Cdks, activating the Cdks kinase activity, enabling them to phosphorylate downstream targets. Once this is accomplished, what happens?

A

Cyclins are degraded and Cdks are thus inactivated

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35
Q

What are the four classes of Cdks?

A
  1. ) G1 Cdk
  2. ) G1/S Cdk
  3. ) S Cdk
  4. ) M Cdk
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36
Q

Promotes passage through the restriction point

A

G1 Cdk

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37
Q

Commits cell to replication

A

G1/S Cdk

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38
Q

Initiates replication

A

S Cdk

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39
Q

Promotes mitosis

A

M Cdk

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40
Q

Act as the molecular switches of the cell cycle

A

Cyclin-Cdk complexes

41
Q

An important aspect of the cell cycle is to inactivate the Cdk-cyclin complexes to ensure that each cellular event is triggered only

A

Once per cell cycle

42
Q

Functions to conrtol the initiation of DNA replication once per cell cycle at replication origins

43
Q

A large multi-protein complex binds to the origins of replication. There are called the

A

Origin Recognition Complex (ORC)

44
Q

Bind to origins throughout the cell and act as landing pads for other regulatory proteins to initiate replication at different positions throughout the genome

A

Origin Recognition Complex (ORC)

45
Q

What is part one of the control of initiation of replication or entry into S phase?

46
Q

Cdc6 is usually present at low levels throughout the cell cycle. but increases transiently in

47
Q

Binds to ORCs, which in turn causes recruitment of the Mcm proteins

48
Q

What types of proteins are the Mcm proteins?

49
Q

All together, the ORC, Cdc6, and Mcm complex is called the

A

Pre-replicative complex (pre-RC)

50
Q

Functions to have the pre-RC poised to replicate the DNA

51
Q

Triggers replication by assembling DNA polymerase at the origin and activating the Mcm proteins

52
Q

What is part two of the control of initiation of replication or entry into S phase?

53
Q

After Cdc6’s activity, the origin is now ready to fire, but it requires the activity of

54
Q

S-cyclin transcription is activated in

55
Q

Forms and activates S-Cdk, which then phosphorylates the pre-RC, activating replication

A

S-cyclin-Cdk complex

56
Q

Also prevents the re-replication of DNA. This is an example of one of the checks and balances that is important for cell control

57
Q

Causes Cdc6 to dissociate from ORC after origin has fired for replication

-results in disassembly of pre-RC

A

Phosphorylation of Cdc6 by S-Cdk

58
Q

The dissociation and phosphorylation of Cdc6 from the ORC also causes its

A

Degredation

59
Q

Also phosphorylates Mcm/helicase proteins and causes their export from the nucleus

60
Q

S-Cdk activity remains high during G2 and mitosis causing the Cdc6 protein to always be phosphorylated, therefore preventing

A

Re-replication

61
Q

Also ensures no re-replication by also phosphorylating Cdc6 and Mcm proteins

62
Q

To allow replication at the end of a cell cycle, all Cdk activity is reduced to zero at the end of

63
Q

Similar to S phase, the M phase is poised and ready to go. It is activated by

64
Q

The regulation of M-Cdk is controlled by which three proteins?

A
  1. ) M cyclin
  2. ) Cdk Activating Kinase (CAK)
  3. ) Cdk Inhibitory Kinase (Wee1)
65
Q

Gradually increases during G2 and M phases due to transcription of the gene

66
Q

When M cyclin binds M-Cdk, the complex is only partially active. It become fully active after phosphorylation by

A

Cdk-activating kinase (CAK)

67
Q

Only partially activate Cdks

68
Q

When M cyclin binds M-Cdk, the complex is only partially active. It become fully active after phosphorylation by CAK. Before the complex can do anything, it is inactivated by

A

Cdk-inhibitory kinase (Wee1)

69
Q

Removes the inhibitory phosphate added by Wee1 and re-activates the complex

-Shows how the M-Cdk complex is poised for activation

70
Q

The M-Cdk compex contains a cyclin, and activating phosphate (from CAK) and an inhibitory phosphate (from Wee1). It is activated when the phosphate from Wee1 is cleaved by Cdc25. This shows how the M-Cdk complex is

A

Poised for activation

71
Q

When the M-Cdk complex is active, it phosphorylates and activates proteins that are important in

A

Assembly of mitotic spindle, chromosome condensation, and breakdown of nuclear envelope

72
Q

One feedback loop that enables more M-Cdk to become activated is that active M-Cdk inhibits

A

Wee1

-prevents inhibition of other M-Cdk’s

73
Q

Another feedback loop that enables more M-Cdk to become activated is that active M-Cdk phosphorylates more

A

Cdc25

-activates more of the phosphatase and leads to more active M-Cdk

74
Q

Exit from mitosis requires inactivation of M-Cdk, which occurs primarily through protein degradation by

A

Ubiquitination

75
Q

The protein that causes M-Cdk degradation is a ubiquitin ligase called

A

Anaphase Promoting Complex (APC)

76
Q

APC is activated by

-A negative feedback loop

A

Active M-Cdk

77
Q

A phase with absolutely no Cdk activity

78
Q

What are the three mechanisms to ensure that there is no Cdk activity in G1?

A
  1. ) Ubiquitin mediated degradation of Cdks
  2. ) Cyclin Kinase Inhibitor (CKI) accumulation
  3. ) Decreased Cyclin Transport
79
Q

In animal cells, decreased cyclin transport is mediated by the

A

Retinoblastoma (Rb) protein and the E2F transcription factor

80
Q

Bind to Cdk-Cyclin complexes and inhibit their activity

A

Cdk Inhibitor Proteins (CKIs)

81
Q

CKI production is increased during

82
Q

A transcription factor that reglates the expression of many genes required for entry into S phase including
G1/S and S cyclins

83
Q

E2F function is controlled in part by the

-binds E2F during G1 and blocks its activity

A

Rb Protein

84
Q

Rb binding E2F during G1 results in downstream genes (i.e. G1/S and S cyclins) not being

A

Transcribed

85
Q

When cells receive and extra-cellular signal to divide, G1-Cdk accumulates and

-reduces affinity of Rb for E2F, which prevents inhibition

A

Phosphorylates Rb

86
Q

Phosphorylates Rb, reducing its affinity to E2F. This then results in the
expression of G1/S and S cyclin

87
Q

Loss of both copies of the Rb gene leads to

A

Retinoblastoma

88
Q

Increases its own expression once released by Rb inactivation

-positive feedback

89
Q

E2F expression leads to production of

-phosphorylates more Rb, thereby releasing more E2F

A

G1/S-Cdk and S-Cdk

90
Q

The increase in G1/S-Cdk and S-Cdk causes the phosphorylation and destruction of

-activates more G1/S-Cdk and S-Cdk

A

Ubiquitin ligases and CKIs

91
Q

The function of the cell cycle is to transmit IDENTICAL genetic information to the daughter cells so that there is not an accumulation of

A

Somatic mutations

92
Q

There are 2 checkpoints in the cell cycle to make sure that DNA is ok. These occur in

A

Late G1 and Late G2

93
Q

In G2, if the DNA is damaged then this sends a signal that blocks

A

Cdc25 activation

94
Q

What happens when activation of Cdc25 is blocked by the G2 checkpoint?

A

M-Cdk is not activates and cell does not progress to mitosis

95
Q

The G1 checkpoint prevents progression into S phase by inhibiting the activation of

A

G1/S-Cdk and S-Cdk complexes

96
Q

The activity of the G1 checkpoint is controlled in part by

97
Q

Stimulates the expression of several genes including the CKI protein p21

98
Q

The CKI then binds G1/S-Cdk and S-Cdk and inactivates them, which

A

Prevents passing of the restriction point

-No S phase entry

BMS (62 decks)

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