Cell Signalling, the Cell Cycle + Cancer Flashcards

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1
Q

When do cells divide?

A

in response to specific molecular signals (typically from growth factors)

receive signals from other molecules

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2
Q

What do cells divide to produce in mitosis?

A

2 identical daughter cells

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3
Q

Why do cells stop dividing?

A

to specialize in structure and function (aka differentiation)

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4
Q

What is differentiation?

A

a process that produces specialized cells (function and structure)

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5
Q

T or F: once differentiated, all cells stop dividing

A

false! some continue to divide under certain conditions

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6
Q

Describe apoptosis

A

programmed cell death - a process that eliminates unnecessary cells during development and removes unhealthy/damaged cells in mature organisms

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7
Q

How must the processes (divide, differentiate, death) occur in relation to one another to ensure a healthy organism?

A

balanced

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8
Q

What is a result of an unbalanced cell cycle?

A

an organism may end up with too few or too many cells which can cause problems of varying severity (ex. hair loss vs. growth of warts into tumours)

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9
Q

Describe the eukaryotic cell cycle

A

a sequence of events that culminate in cell division

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10
Q

What are the cell cycle events regulated by?

A

various checkpoint proteins

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11
Q

What do checkpoint proteins do?

A

stimulate or inhibit cell division until conditions are right to proceed to the next phase of the cell cycle

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12
Q

What generally happens to a cell when it specializes?

A

it stops dividing and ‘exits’ the cell cycle

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13
Q

Describe cancer

A

uncontrolled division of cells that results from an improperly regulated cell cycle

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14
Q

What is the primary defence against cancer for multicellular organisms?

A

the detection of DNA damage (mutations) before division (cell cycle regulation)

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15
Q

How do most cancers exist?

A

because the cells have mutations in genes required for DNA damage detection and arrest of the cell cycle

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16
Q

How many primary cell cycle checkpoints are there in eukaryotes?

A

3

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17
Q

What are the 3 primary cell cycle checkpoints in eukaryotes?

A

G1
G2
M

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18
Q

Describe the G1 checkpoint (what is it and when does it occur)

A

Aka the restriction checkpoint

occurs at the end of G1

checks whether cells are given permission to enter S phase (checks for mutations or whether the environment is favourable)

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19
Q

When does the G1 checkpoint occur?

A

at the end of G1 before cells enter S phase

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20
Q

What things might prevent a cell from passing the G1 checkpoint and entering S phase?

A

if it does not contain permissive instructions to do so

if it has mutations

if the environment is not favourable

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21
Q

What happens to a cell if it does not pass the G1 checkpoint?

A

It will not enter S phase and instead will enter G0 phase

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22
Q

T or F: many cells stay in G0 their entire lives

A

true (ex. neurons and muscle cells)

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23
Q

Describe the G2 checkpoint

A

occurs throughout the S phase or at the end of G2 phase

detects damage or errors in DNA as replication occurs

stops the cell cycle to repair damage before cell enters M phase

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24
Q

When does the G2 checkpoint occur?

A

during S phase and at the end of G2 phase before mitosis

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25
Q

What is the purpose of the G2 checkpoint?

A

to detect damage or errors in DNA while replication is occurring and to stop the cell cycle for repairs to the DNA and/or trigger apoptosis if the damage is too severe

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26
Q

Describe the M checkpoing

A

Aka spindle checkpoint

occurs in metaphase, before anaphase and the separation of chromosomes to make sure each centromere is properly attached to a spindle microtubule

prevents large scale mutations resulting in aneuploidy

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27
Q

When does the M checkpoint occur?

A

At metaphase of the M phase before anaphase pulls apart chromosomes

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28
Q

What is the purpose of the M checkpoint?

A

to make sure each centromere is properly attached to a spindle fibre so that each cell ends up with the correct number of chromosomes when they divide

prevents aneuploidy

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29
Q

What organism was used in this experiment?

A

budding yeast (S. cerevisiae)

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30
Q

Why is budding yeast used in this experiment?

A

because it is a single celled haploid organism which reproduces asexually by mitosis but cytokinesis is not linked to nuclear division so the cells do not divide symmetrically

= cell cycle arrest can be monitored visually with a microscope by observing morphology of the cells

It can reproduce sexually when both alpha and a cells are allowed to fuse to produce the diploid cell and can divide by meiosis

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31
Q

How does budding yeast divide by mitosis?

A

asymmetrically

the mother cells form small buds at S phase which produce smaller daughter cells

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32
Q

What 4 components does every cell signalling pathway share?

A

extracellular ligand

cell-surface receptors for the ligand

intracellular enzymes that send the signal when the ligand binds

cellular response (A change in cellular behaviour or metabolism)

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33
Q

What is signal transduction?

A

the response of cells to signal ligands in their environment

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34
Q

T or F: yeast only undergo asexual reproduction

A

false, they do sexual reproduction too

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35
Q

What are the 2 different mating types of S. cerevisiae?

A

a cells and alpha cells

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36
Q

When will yeast reproduce asexually?

A

in the absence of EITHER a cells OR alpha cells

they only require one

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37
Q

When will yeast reproduce sexually?

A

if both a cells and alpha cells are present

they will fuse into a diploid cell for meiosis

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38
Q

what does sexual mating of yeast cells require of the cell cycle? How do yeast cells make this happen?

A

the cell cycle must be stopped in order for the alpha and a cells to fuse and form a diploid cell

alpha cells release alpha-factor signal ligands to arrest the cell cycle before DNA synthesis (S phase)

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39
Q

How do alpha factors work?

A

alpha cells constantly release this signal ligand (small peptide) that binds to the alpha-factor receptors on the yeast cell surfaces which triggers the arrest of the cell cycle before DNA synthesis (S phase)

they also trigger the transcription of genes required for cell fusion

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40
Q

What kind of cell surface receptor are alpha-factor receptors?

A

G-protein couple receptors (GPCR)

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41
Q

When is the cell cycle stopped if an alpha factor binds to the alpha factor receptor?

A

At the G1 checkpoint in G1 phase (before S phase)

42
Q

What are the 3 cell morphology types we saw in lab?

A

schmoo

dumbbell

buds

43
Q

At what stage of the cell cycle and what checkpoints would you see a schmoo?

A

checkpoint: G1

at the end of G1 phase before S phase

ex. this is when the alpha factor has bonded to the alpha factor receptors on yeast cell surfaces in order to allow the a cells and alpha cells to fuse

44
Q

Describe schmoo morphology

A

large and oblong

45
Q

At what stage of the cell cycle and what checkpoints would you see dumbbells?

A

checkpoint: M phase

46
Q

Describe dumbbell morphology

A

2 cells have formed and they are even sized roughly spherical and touching

47
Q

At what stage of the cell cycle and what checkpoints would you see buds of variable sizes?

A

during S phase or at the end of G2 phase

checkpoint: G2 phase

48
Q

Describe the variable bud morphology

A

cells have large buds of varying sizes with uncondensed chromatin

49
Q

What was the purpose of this lab?

A

to treat yeast with different chemicals to observe the cell morphology at different stages in the cell cycle

50
Q

in this lab, what causes cells to arrest at the G1 checkpoint?

A

the signal transduction with the alpha factor - when it binds to the alpha factor receptors on the cell surface

51
Q

in this lab, what causes cells to arrest at the G2 checkpoint?

A

chemically-induced DNA damage

52
Q

In this lab, What causes cells to arrest at the M checkpoint?

A

chemically-induced damage to the spindle microtubules

53
Q

What was the yeast mutant used in this lab?

A

MAD1

54
Q

Which 3 chemical treatments did we use in lab?

A

alpha factor

hydroxyurea

nocodazole

55
Q

What was hydroxyurea used for in this lab?

A

To induce cell arrest at the S phase by slowing DNA polymerase function

56
Q

What checkpoint did hydroxyurea stop the cell cycle at and what did this result in?

A

Stopped at the G2 checkpoint and made errors during DNA replication

resulted in budding

57
Q

What was nocodazole used for in this lab?

A

inducing damage to the spindle microtubules

58
Q

What checkpoint did nocodazole stop the cell cycle at and what did this result in?

A

stopped the cell cycle at M checkpoint because it damaged spindle microtubules

results in dumbbells

59
Q

What was alpha factor used for in this experiment?

A

it synchronizes the opposite mating type (a cells) in yeast for sexual reproduction

the binding of the alpha factor to the alpha factor surface receptors on the cells causes the cell cycle to stop before DNA replication (before the S phase) in order for cell fusion of the tw o cell types

60
Q

What checkpoint did alpha factors stop the cell cycle at and what did this result in?

A

at the G1 phase

results in schmoos

61
Q

What are regulators?

A

proteins that can stimulate or inhibit cell progression through the cell cycle

62
Q

What are protooncogenes?

A

genes that code for regulatory proteins that stimulate cell progression through the cell cycle

63
Q

What are tumour suppressor genes?

A

genes that encode regulatory proteins that inhibit cell progression through the cell cycle

64
Q

What are the most important cell cycle regulators?

A

cyclin-dependent kinases (CDKs)

65
Q

What is the function of kinases?

A

to phosphorylate things (add a phosphate to things)

66
Q

T or F: CDKs are always present in the cell but not always active

A

true

67
Q

When are CDKs active?

A

when they are bound to cyclin proteins

68
Q

Why does the activity of CDKs depend on cyclin?

A

to be active, CDKs must be bound to cyclin

the concentration of cyclin inside the cell fluctuates depending on the phase of the cell cycle

69
Q

How do CDK-cyclin regulate the progression of cells through the cell cycle?

A

because the concentration of different CDK-cyclins varies and fluctuates throughout the cell and at different stages of the cell cycle

70
Q

If CDK-cycling complexes are activated, what happens to the cell cycle?

A

it is stimulated

71
Q

If CDK-cycling complexes are inactivated, what happens to the cell cycle?

A

the cell cycle is inhibited

72
Q

How do cells progress from the G1 phase into the S phase?

A

growth factors stimulate signals inside cells that cause G1-phase cyclin concentrations to rise

the cyclins bind to CDKs which phosphorylate each other and drive the cell into S phase

73
Q

How are cells inhibited from passing from the G1 phase into S phase?

A

if DNA is damaged, protein p53 inhibits the G1 CDK-cyclin complex which stalls the cycle for DNA to be repaired or to trigger apoptosis

Rb also prevents cells from entering S phase when there’s no growth factor signals (no kinases to phosphorylate them)

74
Q

What does Rb stand for?

A

retinoblastoma protein

75
Q

How would an Rb function if there were growth factors?

A

the growth factors would signal for the production of CDK-cyclin complexes which would phosphorylate the Rb and prevent it from inhibiting progression

76
Q

What type of regulatory genes are the ones that code for CDK and cyclin?

A

protooncogenes

77
Q

What type of regulatory genes are the ones that code for p53 and Rb?

A

tumour suppressor genes

78
Q

How might cancer arise at the G1 checkpoint?

A

if there’s mutations in the tumour suppressor genes that code for p53 or Rb, the inhibition of the cell cycle may occur which may lead to cells with damaged or mutated DNA being replicated

79
Q

What kind of mutations are ones on the tumour suppressor genes that code for p53 and Rb?

A

recessive (must occur on both alleles for cell cycle to be affected)

80
Q

What proteins are involved in stimulating the rise in S-phase cyclins?

A

growth factors

81
Q

What protein would be activated if a DNA strand breaks during replication?

A

ATM protein will halt the cell cycle and stimulate other proteins that can repair the DNA one of which is BRCA1

82
Q

Which stage of the cell cycle would ATM be involved in?

A

S phase

there would be an arrest at the G2 checkpoint

83
Q

What type of genes are the genes that code for ATM and BRCA1?

A

tumour suppressor genes

84
Q

What happens when there’s mutations in the genes that code for the ATM and BRCA1 proteins?

A

higher risk of cancers such as

ATM = leukemia and lymphoma cancers

BRCA1 = breast and ovarian cancer

85
Q

What does ATM stand for?

A

ataxia telangiectasia mutated

86
Q

What does BRCA1 stand for?

A

Breast Cancer 1

87
Q

What proteins stimulate progression from the M checkpoint?

A

M-phase cyclins + CDKs activate a complex called the Anaphase-Promoting Complex/Cyclosome (APC/C)

88
Q

What does APC/C stand for?

A

Anaphase Promoting Complex/Cyclosome

89
Q

What activates the APC/C?

A

M-phase cyclins + CDKs

90
Q

What happens when the APC/C is activated?

A

the attachment of spindle microtubules to the centromeres of chromosomes

91
Q

What does APC/C do if there is an incorrect attachment of spindle microtubules to chromosomes?

A

active APC/C stimulates the destruction of proteins that hold the 2 copies of each chromosome/chromatid together at the centromere so that the chromosomes/chromatids can separate properly during anaphase

92
Q

What are the inhibiting proteins of the M phase?

A

MAD = Mitotic Arrest Deficient proteins

93
Q

What does MAD stand for?

A

Mitotic Arrest Deficient proteins

94
Q

How do MAD proteins function in inhibiting the cell from progressing from metaphase to anaphase?

A

if chromosomes/chromatids are not properly attached to the mitotic spindle, MAD will inhibit APC/C and prevent anaphase

95
Q

What is the goal of MAD?

A

to prevent aneuploidy by stopping anaphase from happening in cells where chromosomes / chromatids are incorrectly attached to mitotic spindles

96
Q

What are mutated versions of proto-oncogenes called?

A

oncogenes

97
Q

What do oncogenes do?

A

they increase stimulation of regulatory proteins and allow for uncontrolled cell division that can lead to cancer

98
Q

What do tumour suppressor gene mutations cause?

A

a loss of inhibition in regulating the cell cycle which can lead to uncontrolled cell division and cancer

99
Q

What do mutations in proto-oncogenes cause?

A

a gain of function

100
Q

Are mutations of proto-oncogenes dominant or recessive? what does this mean?

A

dominant

a mutation in only one allele will produce a protein that puts the cell cycle into overstimulation

101
Q

Are mutations of tumour suppressor genes dominant or recessive? What does this mean?

A

recessive

both alleles must be mutated for the cell cycle to be affected