Strand 4 - Cell cycle Flashcards

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1
Q

the cell cycle requires high…… to ensure stable inheritance?

A

fidelity

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2
Q

which 3 types of cells are found in the G0 phase?

A

terminally differentiated cells
quiescent cells
senescent cells

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3
Q

CDKs are protein kinases which transfer what group onto substrates?

A

a phosphate group

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4
Q

what are CDKs activated by?

A

cyclin proteins

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5
Q

what does APC/C trigger the degradation of?

A

M cyclin

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6
Q

give 2 examples of upstream kinases/phosphatases which are cdk regulators?

A

CAK and Cdc25

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7
Q

give an example of a CDK inhibitory protein

A

p27

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8
Q

APC/C signals to M cyclin to do what?

A

end mitosis and initiate cell division

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9
Q

APC/ is a …… ligase. It covalently attaches …… to M cyclin

A

ubiquitin ligase

attaches ubiquitin

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10
Q

what does SGF signal for the degredation of to promote G1-S transition?

A

degradation of CKIs

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11
Q

what does SGF attach to CKIs?

A

ubiquitin

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12
Q

what does mitogen promote the synthesis of?

A

G1-S cyclin

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13
Q

if there is DNA damage to the cell, what does the G2 checkpoint inhibit?

A

cyclin activity via CKIs

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14
Q

if a chromosome is detected as unattached by the M phase checkpoint, what is prevented?

A

M cyclin destruction

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15
Q

what drives the transition from G1 to S phase?

via activating which molecule?

A

active G1-CDK via mitogen activation

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16
Q

what does the G2 checkpoint check for?

A

if replication is complete, if DNA damage has been repaired, if cell is large enough,

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17
Q

what does the mitotic checkpoint check for?

A

if chromosomes are attached to spindle

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18
Q

if the M phase checkpoint is satisfied, which molecule is activated, causing the degredation of M-cyclin therefore?

A

APC/C

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19
Q

if checkpoints in the cell cycle cannot be satisfied cells can :

A

exit cell cycle terminally
start apoptosis
withdraw from cycle -> senescence

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20
Q

what does abherrant mitogen signalling cause to cells?

A

drives cells through the G1 checkpoint

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21
Q

what can defects in the mitotic checkpoint cause to chromosomes?

A

aneuploidy

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22
Q

which mutation causes cancer predisposition syndrome?

A

BubR1 mutation

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23
Q

which cell type have stopped proliferating?

A

nerve cells/neurons

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24
Q

which 2 receptors can mitogens bind to?

A

EGFR / HER2

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25
Q

when mitogens bind to either EGFR or HER2, which signalling cascade is triggered?

give an example of a gene this pathway causes to be activated

A

Ras - Raf - MapK pathway

Myc

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26
Q

Which cyclin gene does Myc upregulate?

which CDK can this cyclin gene then bind to and activate?

A

cyclin D gene

bind to CDK 4 / 6 (G1-CDK)

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27
Q

Which protein does G1-CDK target?

A

Retinoblastoma protein

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28
Q

which txn factor does retinoblastoma protein bind to?

A

E2F

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29
Q

which cyclins does E2F upregulate?

these cyclins can then bind to CDK2 to form what?

A

E and A

G1-S CDK and S-CDK

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30
Q

what do double stranded breaks in DNA activate, causing the **prevention of G1-CDK **progression into S phase?

A

ATM/R, Chk1/2

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31
Q

which CDK does p21, a CKI, inhibit?

A

G1/S-CDK

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32
Q

which cell structure is duplicated in S phase, as well as DNA?

A

centrosomes

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33
Q

do eukaryotes have one or multiple ORICs?

A

multiple

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34
Q

function of the SSBPs in DNA replication?

A

help strands separate

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35
Q

what does DNA primase do in replication?

A

initiates polymerisation

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36
Q

what do topoisomerisases do in replication?

A

remove supercoils

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37
Q

function of sliding clamp in DNA replication?

A

keeps polymerase on DNA

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38
Q

function of DNA ligase in replication?

A

joins okazaki fragments

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39
Q

telomeres are repeating units of what combo of bases?

A

GGGTTA

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40
Q

telomeres extend which end of a chromosome? 5’ or 3’?

A

3’

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41
Q

damaged DNA bases cause the helix to become what?

A

distorted

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42
Q

NHEJ is performed when what is detected?

A

DNA breaks

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43
Q

where is info used from to repair DNA breaks if the cell is in S or G2?

A

a sister chromosome

44
Q

p53 inhibits which CDK?

A

M-CDK

45
Q

which 2 types of division occur during meiosis?

A

reduction division then an equational division

46
Q

during which phase of mitosis does the nuclear envelope begin to disappear?

A

prometaphase

47
Q

during metaphase, what attaches to the sister chromatids?

A

microtubules

48
Q

during ……. chromosomes condense?

A

prophase

49
Q

during which phase of mitosis does the bi-orientation of the chromosomes on bipolar spindle occur?

A

metaphase

50
Q

the contractile ring which starts to contract during telophase, is made up of which 2 components?

A

actin and myosin

51
Q

entry to mitosis is driven by which CDK?

A

M-CDK

52
Q

Which 2 downstream mitotic kinases does M-CDK regulate?

A

aurora and polo kinases

53
Q

the kinetochore is the binding site on a chromosome for what?

A

microtubules

54
Q

kinetochore proteins are recruited by which 2 kinases in early mitosis?

A

M-CDK and Aurora B

55
Q

in prophase:

cohesin is……..
condensin is…..

A

cohesin removed (from chromosome arms)
condensin recruited

56
Q

what is the function of cohesin molecules in prophase?

A

to hold 2 sister chromatids together

57
Q

……… 1 and 2 co-operate to condense chromosomes in mitosis

A

condensins

58
Q

microtubules are nucleated at which end?

A

minus end

59
Q

microtubules can grow and shrink at which end?

A

the plus end

60
Q

give an example of a nucleating protein in microtubules

A

y-TuRC

61
Q

give an example of a microtubule adaptor protein (MAP)

A

Ndc80 or Nuf2

62
Q

what are the 2 motors, allowing cell components to move along microtubules?

A

kinesin -5
dyenin

63
Q

which ends of microtubules does kinesin walk to?

A

plus ends

64
Q

which end of microtubules does dyenin walk to?

A

minus ends

65
Q

what does kinesin-5 form which allows it to crosslink with microtubules?

A

dimers

66
Q

which molecule moves kinetochores towards the cell equator?

A

CENP-E

67
Q

which kinase detects bi-orientiation via detecting levels of tension (a mechanism not fully understood yet)?

A

aurora B

68
Q

what does aurora B phosphorylate to remove microtubules from kinetochores?

A

Ndc80

69
Q

what does the spindle checkpoint detect?

A

unattached kinetochores

70
Q

which complex do unattached kinetochores produce, which inhibits APC/C, keeping the cell in mitosis?

A

MCC

71
Q

which complex is no longer produced once all kinetochores are occupied with microtubules?

A

MCC

72
Q

the coordinated degredation of which two molecules ensures that biochemical exit from mitosis and the onset of anaphase chromosome movements occur together?

A

M-cyclin and securin

73
Q

during which phase of mitosis do condensins dissociate and cohesins re-associate?

A

telophase

74
Q

which two things in normal stem cells, does asymmetric cell division balance?

A

proliferation and cell cycle termination

75
Q

cell intrinsic ACD occurs in which type of cell?

A

neuroblast

76
Q

cell extrinsic ACD occurs in which type of stem cell?

A

male germline stem cells

77
Q

which two model organisms are ACD core mechanisms learned from?

A

c elegans and drosophila

78
Q

polarization can be either microtubule or……. dependent?

A

RHO1

79
Q

polarization in a drosophila neuroblast can be either from the …….. or the previous division

A

neuroectoderm

79
Q

which group of proteins causes the polarisation of the c.elegans zygote?

A

PAR proteins

80
Q

the positioning of mitotic spindle in all animals is controlled by the molecular machine, composed of which 3 molecules?

A

NUMA
LGN
Dyenin

81
Q

which protein at the anterior side of the cell promotes the degradation of the germ plasm proteins, ensuring somatic specification?

A

MEX-5

82
Q

Which protein directs the localization of staufen, prospero and brat?

A

miranda

83
Q

what is an inhibitor of notch signalling?

A

numb

84
Q

when protooncogenes are mutated, what do they mimic? what do they stimulate?

A

a stuck accelorator stiumulating abherrant cellular growth and division

85
Q

what is the chromosomal instability linked with cancer?

A

aneuploidy

86
Q

what happens to chromosomes following DNA ds breaks?

A

they are translocated or rearranged

87
Q

what are the causes of aneuploidy in mitosis? (write out)

A
  • inappropriate kinetochore-microtubule attachments
  • compromised SAC
  • centrosome overduplication
  • problems with chromosome cohesion
  • tetraploidy due to cytokinesis failure
88
Q

aneuploidy occurs in which 3 cells?

A

hepatocytes, neural progenitors and neurons

89
Q

how can cancer cells tolerate aneuploidy? (3 ways)

A
  • lowering DNA damage response
  • increase replication stress tolerance
  • prolonged mitosis
90
Q

which trisomy is associated with increased proliferation?

A

trisomy 12

91
Q

in which type of cancer do trisomies confer a selective advantage upon stress such as hypoxia?

A

colorectal

92
Q

which chimeric protein is the cause of chronic myeloid leukemia?

A

BCR-ABL

93
Q

what happens to the protooncogene ABL when a cell is forced into the cell cycle?

A

it is aberrantly activated

94
Q

name 3 agents which promote ds DNA breaks, increasing the risk of chromosome translocations in cancer

A

topoisomerase 2 poisons
radiation
CIN

95
Q

ABL is associated with which chromosome in chronic myeloid leukemia?

A

9

96
Q

BCR is associated with which chromosome in chronic myeloid leukemia?

A

22

97
Q

what drug is used for the treatment of ABL (chronic myeloid leukemia)?

A

imatinib

98
Q

the production of which protooncogene promotes cell proliferation and survival in BCR-ABL signalling?

A

MYC

99
Q

the deletion and frameshift mutations that lead to loss of Rb function are observed in which type of tumours?

A

retinal

100
Q

Rb inactivation predisposes patients to defects in which cell growth pathway?

A

p53

101
Q

what are the 3 types of protooncogenes associated with the Rb pathway?

A

growth signals
Wnt
cytokines

102
Q

what is Rb?

A

retinoblastoma = an eye tumour

103
Q

what are the two types of retinoblastoma?

in which type of retinoblastoma are both eyes affected by tumours and the retinoblastoma is inherited?

A

sporadic and familial

familial = both eyes (high risk of other cancers)

104
Q

through the transcription of what…..Rb leads to CIN and aneuploidy?

A

E2F

105
Q

cancer cells have a high tolerance to what?

A

chromosome instabilities