spatial control of cell division Flashcards

1
Q

what is cell division needed for

A

growth, healing and replacing old cells

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2
Q

how many cells are in your body

A

~10 trillion

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3
Q

how often are your whole body of cells replaced

A

1x a year

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4
Q

what are the steps in the cell cycle

A

M phase, G1, S and G2

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5
Q

what do CDKs do

A

they phosphorylate

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6
Q

what to cyclins do

A

tell the CDKs what to phosphorylate (recruit the CDK to the right substrate) (when the cyclin changes, you phosphorylate different proteins in the cell to control different processes)

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7
Q

what does securin do

A

stops protein seperates from being degraded - promotes seperation

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8
Q

what does Mps1 kinase do

A

activates the mitotic checkpoint by localising to the outer kinetochore region to produce a signal

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9
Q

what do kinetochores do

A

produces w signal within the mitotic checkpoint to produce a mitotic checkpoint complex (MCC) which is 4 proteins assembled into a complex

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10
Q

what does aurora b kinase do

A

it is localised in a centromere during error correction

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11
Q

what do centromeres do

A

they phosphorylate the binding sites of microtubules within error correction to destabilise the incorrect microtubule attachments

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12
Q

what are Mps1 kinase and aurora B kinase both controlled by

A

space

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13
Q

what are the stages in the mitotic checkpoint

A
  • mps1 kinase localises to a kintetochore
  • mps1 recruits other proteins and assembles them into an inhibitory complex (MCC)
  • MCC inhibits a large ubiquitin ligase needed for the mitotic exit (the anaphase promoting complex)
  • microtubule attach and the checkpoint signal gets shut down
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14
Q

what does mps1 interact directly with

A

the NDC80 complex in vitro

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15
Q

what is the NDC80 complex required for

A

microtubules to bind kinetochores

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16
Q

what do microtubules compete off in vitro

A

the mps1-ndc80 interaction

17
Q

what enables rapid checkpoint silencing

A

competition between ndc80 and mps1 for microtubules

18
Q

what are the stages in error correction

A
  • aurora b kinase localises to the centromere
  • phosphorylates the kinetochore to remove microtubules (electrostatic charge)
  • kinetochores under tension are removed away from aurora b activity, therefore they are stabilised
19
Q

what can be used to measure live kinase activity

A

FRET reporters

20
Q

centromemre phosphorylation is the same irrespective of what

A

microtubule attachment

21
Q

what is reduced upon microtubule attachment

A

kinetochore phosphorylation

22
Q

what happens if the mitotic checkpoint goes wrong

A

chromosome gain/loss

23
Q

what happens if error correction goes wrong

A

chromosome damage (during cell separation at cytokinesis)

24
Q

what are frequently seen in tumour cells

A

mitotic errors

25
Q

what are the 5 ways that mitosis can go wrong and end up in aneuploidy

A

weakened checkpoint, error correction defects, multipolar spindles, cohesion defects and tertaploidy

26
Q

which percentage of tumours are aneuploid

A

80-90%

27
Q

what do frequent erros in mitosis cause

A

chromosomal instability

28
Q

what does a degree of chromosomal instability positively correlate to

A

poor patient prognosis, metastasis and resistance to chemotherapeutics

29
Q

what drives darwinian-style tumour evolution

A

genetic heterogeneity