Cell Cycle Regulation and Cancer. Flashcards
1
Q
Define cytokinesis?
A
The point of mitosis where the cytoplasm is divided, forming 2 identical daughter cells.
2
Q
Define a kinase enzyme?
A
An enzyme which phosphorylates proteins.
3
Q
Define meiosis?
A
A type of cell division that results in the formation of 4 haploid gametes.
4
Q
Define mitosis?
A
Cell division that occurs in somatic cells and results in the formation of 2 daughter cells from 1 parent cell.
5
Q
Define a phosphatase enzyme?
A
An enzyme that de-phosphorylates proteins.
6
Q
Define a quiescent cell?
A
A cell that is not dividing but has the ability to divide.
7
Q
Define a somatic cell?
A
Any cell within the body that is not a reproductive cell.
8
Q
Define a transcription factor?
A
A protein that is involved in transcription.
9
Q
What is the cell cycle defined as?
A
The time taken between 2 cell divisions.
10
Q
What are the 3 primary stages that make up the cell cycle?
A
Interphase.
Mitosis.
Cytokinesis.
11
Q
What are the 4 stages of mitosis?
A
Prophase.
Metaphase.
Anaphase.
Telophase.
12
Q
What is cytokinesis?
A
The point of the cell cycle where the dividing cell is cleaved into 2 daughter cells.
13
Q
How many pairs of chromosomes are found in a cell?
A
23 pairs.
14
Q
The cell cycle is the time that is taken between waht 2 events?
A
The cell cycle is the time that elapses between the formation of cell and the division of the same cell.
15
Q
What kind of cells are produced by mitosis?
A
Somatic cells.
16
Q
What kind of cell division produces sex cells or gametes?
A
Meiosis.
17
Q
What is the end product of meiosis?
A
4 non-identical daughter cells, all of which are haploid.
18
Q
How is a diploid cell created from a haploid gamete?
A
A fertilisation, the zygote that is created by the union of egg and sperm will be diploid.
This is because it receives half its chromosomes from the mother and half from the father.
19
Q
What is the major difference between mitosis and meiosis?
A
Mitosis results in the formation somatic cells and meiosis result the formation of gametes.
In meiosis chromosomes take part in step known as synapsis.
20
Q
What is synapsis that occurs during meiosis?
A
Where the homologous chromosomes pair up and form tetrads.
21
Q
Does synapsis and crossing over occur in mitosis?
A
No.
22
Q
When does crossing over occur during meiosis?
A
During synapsis.
23
Q
What is crossing over?
A
Where genetic information is exchanged between chromosomes.
24
Q
How many cycles of cell division take place during meiosis?
A
2 separate cycles of cell division.
25
What happens during the first division of meiosis?
2 diploid cells are formed.
26
What happens during the second division of meiosis?
4 haploid cells are formed.
27
How many cell divisions occur in mitosis?
1.
28
What are the mitotic phase and cytokinesis collectively known as?
M phase.
29
What phase is the majority of the cell cycle dominated by?
Interphase.
30
What are the 3 sub-phases that interphase is divided into?
G1 phase (first growth phase).
S phase (synthesis phase).
G2 phase (second growth phase).
31
What is the main characterisitc of interphase?
The cell will grow much larger in size.
32
Does cellular growth occur in any particular stage of interphase?
Growth occurs in all 3 phases.
33
What happens in G1 phase of interphase?
The centrioles will replicate.
34
What happens in S phase of interphase?
The DNA will replicate.
35
What happens in G2 phase of interphase?
The final growth before meiosis occurs.
36
What is the only point in mitosis where DNA will be replicated.
S phase of interphase.
37
What are cell cycle checkpoints used for?
To ensure that cellular replication occurs properly.
38
What will cell cycle checkpoints mainly search for?
For mutations within DNA replication and to ensure that the cellular machinery is been correctly assembled.
39
What disease could DNA mutations lead to?
Cancer.
40
Is the the cell cycle regulated by intrinsic or extrinsic control mechanisms?
It is regulated by both internal and external control mechanisms.
41
Can the cell cycle stop part way through the cell cycle?
Yes, the cell cycle can stop at a particular checkpoint until a go-ahead signal is received.
42
What are the 4 checkpoints that are found in the cell cycle?
G1/S checkpoint.
G2/M checkpoint.
M checkpoint.
G0 quiescence.
43
What happens at the G1/S checkpoint?
The cell checks to see if the environment is favourable for division and it will monitor the size and integrity of DNA.
44
What happens if DNA is damaged during the G1/S checpoint?
Apoptosis will occur.
45
What happens at the G2/M checkpoint?
The cell monitors DNA replication and checks for any damage or mistakes in the newly synthesised DNA.
46
What happens at the M checkpoint?
The cell monitors the formation of the spindle and the attachment of the spindle to the kinetochores.
47
What happens during mitosis if the chromosomes are not properly aligned on the metaphase plate?
Then mitosis will not happen.
48
What is the G0 or quiescence checkpoint?
The G0 quiescence makes the final decision as to whether to exit the cell cycle or to start again.
49
Which scientists discovered the cell cycle in 2001?
Lee Hartwell.
Paul Nurse.
Tim Hunt.
50
What was Hartwells contribution to the discovery of the cell cycle?
He used budding yeast to to identify the various mutants that blocked the cell cycle.
51
What are cyclins and cyclin dependent kinase’s (CDK’s)?
A group of regulatory proteins that help to regulate the cell cycle.
52
What are cyclins?
Independent proteins.
53
What are CDKs?
Kinase enzymes which depend on cyclin proteins.
54
When does the intracellular concentrations of cyclin proteins tend to increase?
At the end of each stage of the cell cycle.
55
When will CDK enzymes be present in the cell?
They are always present in the cell.
56
What activates CDK enzymes?
The increase in cyclin proteins in the cell activates CDK’s and once activated they will bind to the cyclin proteins.
57
What is the complex that is created by the binding of the CDKs to the cyclin proteins known as?
The MPF (maturation promoting factor).
58
What happens as the cellular concentration of MPF rises?
It will trigger cell division to go on to the next stage.
59
What happens to MPF complexes after the cell cycle has moved on to the next stage?
The cyclin proteins are degraded until the next checkpoint where cyclin concentration will rise again.
60
What kind of cyclins bind to CDK's at the end of G1/S phase?
They will bind to G1/S cyclins.
61
G1/S cyclins help the cell cycle progress from what stage to what stage?
From G1 phase to S phase.
62
What kind of cyclins bind to CDK's during S phase?
S cyclins.
63
What will S cyclins signal for in the cell cycle?
For DNA replication can begin.
64
What happens in the cell cycle when DNA replication is complete?
The cell can move into the G2 phase.
65
What kind of cyclins bind to CDK's at the end of M phase?
M cyclins.
66
What will M cyclins signal for in the cell cycle?
For mitosis to go ahead.
67
Where are G1 cyclins usually found?
Within most cells.
68
What is the job of G1 cyclins?
They help the cell to leave G1 phase and enter S phase by controlling G1/S cyclins.
69
What are the methods of regulating CDK's?
The binding of CDKs to cyclins.
Stimulatory phosphorylation.
Inhibitory phosphorylation.
Binding of inhibitory proteins.
70
When does the binding of CDK's to cyclins help to regulate CDKs?
After the cyclin has bound to the CDK.
71
Is the CDK fully active after it has bound to the cyclin protein?
No.
The binding of the cyclin to the CDK only partially activates the CDK.
72
How is the CDK fully activated after it has bound to the CDK?
Once binding has occurred, an enzyme called CDK activating kinase phosphorylates a site on the CDK enzyme.
This phosphorylation results in a conformational change within the CDK and activates the CDK.
73
How can CDKs be inhibited via phosphorylation?
CDK’s contain 2 other additional phosphorylation sites and when they are phosphorylated it leads to the inhibition of the CDK.
74
What enzyme adds the inhibitory phosphates to the CDK?
An enzyme called wee-1-kinase.
75
What happens when the inhibitory phosphate is added to the CDK by wee-1-kinase?
They will override the stimulatory phosphate that is added by CDK activating kinase.
76
What enzymes will remove the inhibitory phosphates?
They are removed by an enzyme called CDC-25 phosphatase.
77
How can inhibitory proteins help to regulate CDKs?
Inhibitor proteins bind to the MPF complex and this prevents the cell cycle from continuing until the inhibitor is removed.
78
How can inhibitor proteins prevent the MPF complex from forming?
Sometimes inhibitor proteins will bind to the CDK and this prevents the MPF complex from forming.
79
What kind of method will lead to the degradation of cyclin-CDK complexes?
It is a ubiquitin dependent method.
80
How does the ubiquitin method destroy CDKs?
Ubiquitin ligase enzymes add ubiquitin groups to specific amino acids within the cyclin proteins.
Ubiquitins are recognised by the proteasome and this protein will destroy the cyclin protein.
81
Proteins that are ubiquitinated are said to be in what state?
They are said to be polyubiquitinated.
82
How does the proteasome break down cyclin proteins?
It breaks them down into their individual amino acids which can then be recycled.
83
The process of breaking down cyclin proteins is known as what?
As proteolysis.
84
What are the 2 methods of controlling the proteolysis of cyclin proteins?
Via SCF.
Via the anaphase promoting complex.
85
How does the SCF complex control the proteolysis of cyclin proteins?
It controls the degradation of the inhibitor protein which binds to the CDK if the cell is not ready to move onto the next stage in the cell cycle.
86
How is the inhibitor protein that binds to the CDK be degraded?
By poly-ubiquitination.
87
What is the first stage of the degradation of the CDK inhibitor?
The inhibitor protein is phosphorylated by a kinase enzyme and this allows the SCF complex to recognise IT.
88
What happens after the CDK inhibitor protein has been phosphorylated?
The SCF complex and it adds poly-ubiquitin chain to the CDK inhibitor.
89
What is the anaphase promoting complex also known as?
As the cyclostome.
90
What will the anaphase promoting complex be used to destroy?
It destroys the M-cyclin which is part of the PDK complex that allows a cell to go from metaphase to anaphase.
91
What activates the anaphase promoting complex?
An activating subunit called CDC-20 binds to the inactive APC/C complex and this leads to an active APC/C complex.
92
When is the anaphase promoting complex activated?
Once the cell is ready to proceed from metaphase to anaphase.
93
What happens when the APC/C complex has been activated?
It recruits the E1 and E2 ubiquitination enzymes and these will ubiquitinate the M-cyclin protein.
This allows the proteasome complex to recognise and degrade the M-cyclin.
94
When does the regulation of DNA replication begin?
In G1 phase.
95
What is the first step of the regulation of DNA replication in G1 phase?
A complex of proteins known as the origin recognition complex (ORC) binds to the origin of replication (ORI).
96
What is the second step of the regulation of DNA replication in G1 phase, after the ORC proteins have bound the ORI?
2 proteins called CDC-6 and CDT-1 will also bind to the ORC.
97
What is the third step of the regulation of DNA replication in G1 phase, after CDD-6 and CDT-1 have bound to the ORC?
DNA helicase can come and bind to the DNA strands.
98
What is the collection of proteins that are bound to the ORC during the regulation of DNA replication in G1 phase?
As the pre-replicative complex.
99
What proteins are part of the pre-replicative complex?
DNA helicase.
CDC-6 and CDT-1.
The ORI recognition complex.
100
What is the fourth step of the regulation of DNA replication in G1 phase, after the pre-replicative complex has been formed?
An S-CDK complex molecule will bind to the DNA strands.
101
How is an S-CDK complex formed?
When an S-cyclin binds to a CDK molecule.
102
What happens when S-CDK molecules bind to the DNA strand?
It marks the beginning of S phase.
103
What is the first step of the regulation of DNA replication in S phase, after the pre-replicative complex has been formed?
The kinase section S-CDK phosphorylates the CDC-6 proteins and this causes them to fall off the protein complex.
104
What is the second step of the regulation of DNA replication in S phase, after the CDC-6 proteins have been removed from the pre-replicative complex?
The kinase section of S-CDK will phosphorylate the ORC complex.
105
What happens during the regulation of DNA replication in S phase after the ORC complex has been phosphorylated?
It acts as a signal for a protein called the pre-initiation complex to bind to the pre-replicative complex.
106
What is the third step of the regulation of DNA replication in S phase, after the pre-initiation complex has bound the pre-replicative complex?
It allows for the replication fork to be formed and for DNA polymerase to begin DNA replication.
107
What are M cyclins?
The cyclins that are present in M phase.
108
What is the first step of the regulation of sister chromatid separation?
An enzyme called CDK activating kinase (CAK) phosphorylates and activates the M cyclin/CDK complex.
109
What is the second step of the regulation of sister chromatid separation, after the M-cyclin/CDK complex has been activated?
The WEE-1 enzyme phosphorylates the M cyclin/CDK complex and this inhibits the complex.
110
What is the third step of the regulation of sister chromatid separation, after the M-cyclin/CDK complex has been inhibited by WEE-1?
The cell gets to the point in the cell cycle where the M cyclin/CDK complex can become active.
It then signals for the removal of the phosphate group that was added by WEE-1 and the complex is activated.
111
How is the phosphate group that was added by WEE-1 to the M cyclin/CDK complex removed?
A CDC-25 phosphatase enzyme is phosphorylated and then removes the phosphate group.
112
What is the fourth step of the regulation of sister chromatid separation, after the M-cyclin/CDK complex has been activated by the CDC-25 phosphatase?
The M cyclin/CDK will assemble the spindles for chromatin separation during mitosis.
This process also activates the anaphase promoting complex (APC).
113
How does the activation of the M cyclin/CDK complexes affect the number of M cyclin/CDK complexes within the cell?
The activation of the M cyclin/CDK complex tells the cell to make more M cyclin/CDK complex’s.
114
The control of mitosis requires the presence of what?
An activated M cyclin/CDK complex.
115
What is the master control gene for mitosis?
M-cyclin.
116
What 5 mitotic processes will be regulated by M cyclin?
Assembly of the spindle apparatus.
Chromosome condensation.
Breakdown of the nuclear envelope.
Changes in the cytoskeleton.
The re-organsisation of the Golgi apparatus.
117
What will the activation of the APC/C rigger?
Sister chromatid separation.
118
What holds the sister chromatids together during metaphase?
A protein complex known as cohesin.
119
At what stage of the cell cycle do the sister chromatids need to be separated from one another?
As the cell proceeds into anaphase.
120
What is the first step of the separation of the sister chromatids?
The activation of the APC/C complex.
121
How is the APC/C complex activated?
When a CDC-20 protein binds to the inactive form of the APC/C.
122
What is the second step of the separation of the sister chromatids, after the APC/C complex has been activated?
The APC/C complex ubiquitinates a protein called securin which is bound to an inactive separase enzyme.
123
What is the third step of the separation of the sister chromatids, after the APC/C complex has ubiquitinated securin?
Separase is activated and it will cleave the cohesin complex which holds the chromosomes together.
This allows the chromosomes can be separated.
124
What happens during chromosome separation if the spindle fibres have not correctly attached to a chromosome?
A regulatory protein called MAD-2 binds to the chromosome that is not attached to a spindle protein and this causes mitosis to stop.
125
How does MAD-2 prevent sister chromatid separation if a centromere has not bound to a chromosome?
It prevents the CDC-20 protein from binding to the APC/C complex and separase remains inhibited.
126
What happens to the MAD-2 protein when the missing spindle attaches to the chromosome?
MAD-2 will detach from the chromosome and mitosis can continue.
127
What are the 6 basic steps of regulation of mitosis?
M cyclin accumulates and forms complexes with CDK.
M-CDK is phosphorylated, but remains inactive.
M-CDK is activated by CDC-25.
Active M-CDK phosphorylates a variety of proteins.
M cyclin is degraded by the APC complex and M-CDK is deactivated.
The cell exits mitosis and undergo cytokinesis.
128
When will M-cyclins be synthesised?
In S phase.
129
What are the 3 target proteins that are phosphorylated by the active M-CDK complex?
Nuclear lamin proteins.
Histone H1.
Microtubule associated proteins.
130
The phosphorylation of nuclear lamin proteins by the active M-CDK complex leads to what?
Degradation of the nuclear envelope.
131
The phosphorylation of histone H1 by the active M-CDK complex leads to what?
Chromosome condensation.
132
The phosphorylation of microtubule associated proteins by the active M-CDK complex leads to what?
The formation of the spindle.
133
What happens if the cell cycle is unregulated?
It can lead to the uncontrolled division of cells and this can lead to cancer and maybe death.
134
What happens when the tumour suppressing gene is activated?
It leads to the formation of a protein known as the retinoblastoma protein (Rb protein).
135
What is the job of the retinoblastoma protein?
It helps to maintain G1 phase in the cell cycle by keeping the protein E2-F in an inactive state.
136
What is the E2-F protein also known as?
As the gene regulatory protein.
137
What kind of molecule is the E2-F protein?
A transcription factor.
138
By keeping the cell in G1 phase, what is the retinoblastoma protein doing?
Preventing transcription from occurring.
If RB was not present, transcription could continue and this would lead to an unregulated cell cycle.
139
How does the Rb protein prevent transcription from occurring?
By binding to the transcription factor E2-F until the cell to enter S phase.
140
What happens to the Rb/E2-F complex when the cell is ready to enter S phase?
An active G1-CDK enzyme phosphorylates the Rb protein.
This releases the E2-F protein and allows it to act as a transcription factor in DNA replication.
141
What happens to the cell cycle when DNA damage occurs?
The cell cycle will be stopped until the DNA damage is repaired.
142
What happens during the cell cycle when the cell realises that DNA damage has occurred?
Certain kinase enzymes will phosphorylate the P53 protein which is part of the MDM2/P53 complex.
143
What happens during the cell cycle when the cell realises that DNA damage has occurred, after P53 has been phosphorylated?
The P53 protein dissociates from the MDM2/P53 complex and binds to the P21 protein.
144
What happens during the cell cycle when the cell realises that DNA damage has occurred, after P53 has bound to the P21 protein?
A gene is tranacribed and the protein that is produced is a CDK inhibitor protein.
145
What happens during the cell cycle when the cell realises that DNA damage has occurred, after the CDK inhibitor protein has been produced?
The active CDK-inhibitor protein binds to the active G1-CDK complex and inhibits G1-CDK from functioning.
This prevents the cell from proceeding from G1 to S phase.
146
What protein binds to cells in a quiescent state to stop them from dividing?
The RB protein.
147
How can viruses stop the RB protein from halting cell division?
They can produce a type of viral protein called E7 which mimics the protein that usually binds to the RB protein.
148
What happens if the RB protein binds to the E7 viral protein?
The cell proliferation factor is always active and this leads to constant cell division and cancer.
149
What will the viral protein E6 bind to?
The P53 protein.
150
What happens when the viral protein EG binds to P53?
It prevents P53 from binding to P21.
This means no inhibitor can be produced when DNA is damaged and the cell will divide uncontrollably.
