Cell Cycle Control, Cell Growth Regulation, and Cell Death Flashcards

1
Q

what is the most basic function of the cell cycle

A

to accurately replicate DNA

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2
Q

what is the duration of the cell cycle

A

it varies depending on cell type

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3
Q

what are the phases in the eukaryotic cell cycle

A
  • M phase mitosis and cytokinesis
  • S phase DNA replication
  • G1 and G2 phases cell growth
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4
Q

where are the main cell cycle checkpoints

A
  • late G1 phase
  • G2 to M phase
  • Mid M phase
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5
Q

what is checked at the late G1 phase checkpoint

A

ensures favourable environment before DNA replication

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6
Q

what is checked at the G2 to M phase checkpoint

A

confirms DNA is undamaged and fully replicated

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7
Q

what is checked at the mid M phase checkpoint

A

chromosomes are appropriately attached to the mitotic spindle before separation

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8
Q

what is the core of the cell cycle control system

A
  • a series of molecular switches that operate in a defined sequence
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9
Q

how is cell cycle machinery regulated

A
  • phosphorylation kinases (type of enzyme that adds phosphates to other molecules)
  • dephosphorylation phosphatases
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10
Q

how are the kinases regulated in cell cycle control

A

by another set of proteins called cyclins

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11
Q

the kinases involved in cell cycle control are referred to as what

A

cyclin-dependent kinases (Cdks)

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12
Q

the ______ of Cdks is cyclical and the ______ of cyclins is cyclical

A
  • activity
  • concentration
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13
Q

what does G1-Cdk do

A

drive progress through G1 toward S phase

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14
Q

what does G1/S-Cdk do

A

initiate transition into S phase

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15
Q

what does S-Cdk do

A
  • launch S phase
  • trigger DNA replication
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16
Q

what does M-Cdk do

A
  • triggers entry into M phase
  • mediate many changes during itosis
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17
Q

what is a cyclin

A

set of proteins that regulate Cdks

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18
Q

which cyclin is used for G1-Cdk

A

cyclin D

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19
Q

which cyclin is used for G1/S-Cdk

A

cyclin E

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20
Q

which cyclin is used for S-Cdk

A

cyclin A

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21
Q

which cyclin is used for M-Cdk

A

cyclin B

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22
Q

the [ ] of cyclin ____ due to continual transcription and protein synthesis

A

increases

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23
Q

the [ ] of cyclin increased due to what

A

continual transcription and protein synthesis

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24
Q

the [ ] of cyclin ____ due to targeted degradation via ubiquitylation

A

decreases

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25
Q

the [ ] of cyclin decreases due to what

A

targeted degradation via ubiquitylation

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26
Q

the activity of Cdks can be modulated by what

A
  • inhibitor proteins
  • these block the assembly or activity of cyclin-Cdk complexes
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27
Q

cyclin-Cdk complexes contain what key thing that needs to be removed to make them active

A
  • inhibitory phosphates
  • they are removed by phosphatases
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28
Q

what are some roles of protein phosphatases

A
  • removing inhibitory phosphates from cyclin-Cdk complexes to activate them
  • reverse downstream effects of Cdks by removing phosphates that Cdks add to their targets
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29
Q

are protein phosphatases regulated

A
  • yes
  • including by cyclin-Cdk complexes
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30
Q

what is used in the cell cycle to pause the cycle in various ways

A
  • inhibitor proteins
  • phosphate regulation
  • cyclin regulation
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31
Q

what happens if the environment is not favourable for the cell cycle

A

Cdk inhibitors block entry into cell cycle

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32
Q

what happens if DNA replication is not complete

A

inhibition of activating phosphatase Cdc25 blocks entry to mitosis

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33
Q

what happens if there is DNA damage

A

inhibition of activating phosphatase Cdc25 blocks entry to mitosis

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34
Q

what happens if chromosomes are not properly attached to the spindle

A

inhibition of APC/C activation delays completion of mitosis

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35
Q

are Cdks stable or unstable in early g1 phase

A

stably inactive

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36
Q

what happens when conditions are suitable in g1 phase

A

the cell can transition into S-phase and through the rest of the cell cyclel

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37
Q

what happens when conditions are not suitable in G1 phase

A
  • cell-cycle machinery can transiently hold the cell in G1
  • or enter a more prolonged nonproliferative state G0
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38
Q

what happens to the machinery active in late M phase as the cell re-enters G1 phase

A

must be inactivated

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39
Q

what do mitogens do

A

activate signaling pathways that stimulate the synthesis of cyclins and other proteins involved in DNA synthesis/ chromosome duplication

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40
Q

what does accululation of cyclins synthesized by mitogens do

A

will lead to G1/S-Cdk activity to allow progress into S phase

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41
Q

some cells will only divide upon stimulation from extraceullular signals called what

A

mitogens

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42
Q

what happens in G1 when there is DNA damage

A
  • leads to an increase in [ ] and activity of p53, a transcription regulator
  • p53 then activates transcription of a protein called p21- Cdk inhibitor
  • p21 prevents entry into S phase and allows time for DNA repair before replication
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43
Q

how ong can cells delay cell cycle progression

A

temporarily or permanently

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44
Q

when do many cells in the human body stop dividing

A

once they differentiate

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45
Q

what happens to many cells in the human body once they differentiate

A
  • stop dividing
  • dismantle the cell cycle control system
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46
Q

what happens when cells enter G0

A
  • are in an arrested state
  • retain the ability to reassemble the cell cycle control system
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47
Q

what phase does DNA replication happen in

A

S phase

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48
Q

what happens in S phase

A

DNA is replicated w extreme accuracy to prevent mutations

49
Q

how many times is the genome duplicated and why

A
  • only once
  • to prevent damage from gene amplification
50
Q

where does preparation for DNA replication begin

A

early g1

51
Q

what happens in early g1 regarding DNA

A
  • chromosome configuration
  • origin recognition complexes recruit Cdc6 to that helicase can open the double strand
52
Q

what happens in S phase regarding DNA replication

A
  • DNA helicase is activated
  • promotes recruitment of the proteins involved in DNA synthesis
  • prevents re-replication by phosphorylating Cdc6 and the origin recognition complexes
53
Q

what happens if DNA replication is incomplete

A

entry into M phase will be delayed

54
Q

what happens during G2 phase

A

cell continues to grow and prepare for M phase

55
Q

what happens regarding M-Cdk complexes during g2 phase

A
  • they accumulate throughout G2
  • are not active until the end of G2 to help transition into M phase
56
Q

what happens in late G2 phase

A
  • the phosphatase Cdc25 removes inhibitory phosphates to activate M-Cdks which in turn indirectly activates more Cdc25
  • active M-Cdk complexes suppress inhibitory kinases
  • M-Cdks also turn on APC/C
57
Q

what happens when M-Cdks turn on APC/C in late G2 phase

A

eventually directs the degredation of M-cyclin, inactivation of M-Cdks, and exit from M phase

58
Q

what happens during interphase

A
  • cell size increases
  • chromosomes are replicated
  • centrosome is duplicated
59
Q

what are the two phases of M phase

A
  • mitosis nuclear division
  • cytokenesis cytoplasmic division
60
Q

what are the stages of mitosis

A
  • prophase
  • prometaphase
  • metaphase
  • anaphase
  • telophase
61
Q

what happens during prophase

A
  • duplicated chromosomes condense in the nucleus
  • mitotic spindle assembles between the 2 centrosomes
  • centrosomes begin to move apart
62
Q

what is required to ensure duplicated chromosomes are properly segregated during mitosis

A
  • cohesins
  • condensins
63
Q

what do cohesins do

A

assemble along DNA as it is replicated to hold sister chromatids together

64
Q

what do condensins do

A

reorganize and condense each sister chromatid into discreet structures

65
Q

what happens during chromosome condensation

A
  • cohesion rings are partially removed
  • this alows the sisters to remain associated but safely pull apart in later mitosis
66
Q

after chromosome condensation, what assembles

A
  • mitotic spindle
  • contractile ring
67
Q

what is the mitotic spindle composed of and what does it do

A
  • comprised of microtubules and associated proteins
  • pulls duplicated chromosomes apart
68
Q

what is the contractile ring composed of and what does it do

A
  • comprised of actin and myosin filaments around the equator
  • splits the cell in 2
69
Q

when does centrosome duplication occur

A
  • begins in S phase
  • completed by the end of G2 phase
70
Q

what is centrosome duplication initiated by

A
  • same Cdks that initiate DNA replication
71
Q

when are the poles of the mitotic spindle formed

A
  • prophase
  • two centrosomes move to opposite sides of the nucleus
72
Q

what is radiated out of the centrosome

A

an array of microtubules called an aster

73
Q

what happens during prometaphase

A
  • phosphorylation of nuclear pores and lamina
  • breakdown of the nuclear envelope into small membrane vesicles
  • chromosomes attach to spindle microtubules and undergo active movement
74
Q

what prevents the spindle microtubules from making contact with the chromosomes in prophase

A

the nuclear envelope

75
Q

what happens once the nuclear envelope breaks down in prometaphase

A

microtubules attach to the chromosome at the kinetochores

76
Q

when do kinetochores assemble at the centromere

A

prophase

77
Q

where are kinetochores located on sister chromatids

A
  • each chromatid has one
  • they face in opposite directions
78
Q

what happens once the microtubules attach to the kinetochores

A
  • the chromosomes are oriented under tension
  • which signals that they are ready to be separated
79
Q

when does dynamic instability rises and why

A
  • at the start of mitosis
  • partially due to M-Cdk mediated phosphorylation of proteins that influence microtubule stability
80
Q

what are 3 kinda of microtubules

A
  • astral
  • interpolar
  • kinetochore
81
Q

what do astral microtubules do

A

position the centrosomes at the poles via attachment to the cell cortex

82
Q

what are interpolar (non kinetochore)

A
  • microtubules in a constant state of flux
  • form the basic framework of the mitotic spindle along w associated proteins
83
Q

what do kinetochore microtubules do

A

encounter and attach to the chromosomes

84
Q

what happens during metaphase

A
  • chromosomes align at the equator
  • kinetochore microtubules keep each chromosome under tension from attachment at opposite poles
85
Q

what happens during anaphase

A
  • sister chromatids separate and are pulled towards poles
  • kinetochore microtubules get shorter, and the spindle pores move apart contributing to segregation
86
Q

when are cohesions broken down and why

A
  • start of anaphase
  • allows the sisters to be pulled apart
87
Q

what allows cohesion linkages to be degraded

A
  • protease called separase
  • held in an inactive state by inhibtory protein called securin
  • securin is degraded by APC/C so separase can be free to sever cohesion linkages
88
Q

what happens to kinetochore microtubules when chromatids separate

A

they shorten via loss of tubulin subunits

89
Q

what happens in anaphase A

A
  • the sister chromatids are pulled toward opposite poles as the kinetochore microtubules depolymerize
  • The force driving this movement is generated mainly at the kinetochore
90
Q

what happens during anaphase B

A
  • force between non-kinetochore microtubules from opposite poles…
  • pushes and pulls the poles apart
91
Q

what is the driving force in anaphase B

A
  • kinesin act on overlapping non-kinetochore microtubules, sliding them past one another (push)
  • dyneins anchored to the plasma membrane, move along the astral microtubules (pull)
92
Q

what happens during telophase

A
  • chromosomes arrive at poles
  • new nuclear envelope forms around each set
  • division of the cytoplasm begins w the assembly of the contractile ring
93
Q

what happens once the chromosomes arrive at the poles

A
  • vesicles of nuclear membrane surround the chromosome clusters and fuse to reform the nuclear envelope
  • nuclear pores and lamina are dephosphorylated
94
Q

what happens once the nuclear envelope is reformed

A
  • nuclear pores restore the localization of cytosolic and nuclear components
  • chromosome decondence
95
Q

when does cytokinesis occur

A
  • begins in anaphase
  • is not completed until the 2 daughter nuclei have reformed in telophase
96
Q

where does the plane of cleavage occur

A

perpendicular to the axis of the mitotic spindle

97
Q

what is the contractile ring made up on

A

actin and myosin filaments

98
Q

what divides a cell in 2

A
  • sliding of actin against myosin generates the force
  • as the ring contracts, it becomes smaller and eventually disassembles once the cell is split
99
Q

how is the ER segregated during cell division

A

cut in 2 during cytokinesis

100
Q

how is the golgi segregated in cell division

A

fragmented and distributed via motor proteins

101
Q

how are mitochondria/ chloroplasts segregated in cell division

A

inherited randomly

102
Q

how is the number of cells in a multicellular organism regulated

A
  • rate of cell division
  • rate of cell death
103
Q

if cells are no longer needed, what happens

A

they enter programmed cell death (apoptosis)

104
Q

what happens during development regarding toes and fingers

A

cells between them die

105
Q

what happens when a cell dies of acute injury

A
  • it releases their contents across their neighbours
  • triggers a potentially damaging inflammatory response
106
Q

what is cell necrosis

A

a cell dying of acute injury (typically accidental)

107
Q

what is apoptosis

A

programmed/ intentional cell death

108
Q

what happens when a cell dies of apoptosis

A
  • cell collapses and the cell surface is altered to attract phagocytic cells- macrophages
  • cell is engulfed before it can release its contents and trigger an inflammatory response
109
Q

what is the difference between apoptosis and necrosis

A
  • apoptosis intentional/ programmed death
  • necrosis accidental
110
Q

the molecular machinery responsible for apoptosis is what

A

a family of proteases called caspases

111
Q

what are caspases used for

A

the molecular machinery responsible for apoptosis

112
Q

which caspases work together to take a cell apart

A
  • initiator caspases activate downstream
  • executioner caspases dismember numerous key proteins in the cell
113
Q

describe an example of caspases at work

A

degrade lamins to cause irreversible breakdown of the nuclear lamina which allows nucleases to enter the nucleus and degrade DNA

114
Q

what are the main family of proteins that regulate the activation of caspases

A

members of the Bcl2 family

115
Q

what do Bax and Bak do

A
  • promote cell death
  • by inducing the release of cytochrome c from the mitochondria to the cytosol
116
Q

what are two members of the Bcl2 family that promote cell death

A

Bax and Bak

117
Q

what members of the Bcl2 family prevent apoptosis and how

A
  • others including Bcl2
  • preventing the action of Bax and Bak
118
Q

how can cell death be mediated by extracellular signals

A
  • from neighbouring cells or the environment
  • directly via cell surface receptors which trigger a caspase cascade
  • or due to lack of extracellular signaling
119
Q
A