cell cycle Flashcards

cell cycle checkpoints: Explain the effects of internal checkpoints on the regulation of the cell cycle and recall examples.

1
Q

how does the cell transition out of metaphase

A

goes through spindle assembly checkpoint

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2
Q

what 2 things are sensed in spindle assembly checkpoint

A

completion of chromosome alignment, completion of spindle assembly (monitors kinetochore activity as unattached)

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3
Q

what 2 things are required for spindle assembly checkpoint

A

CENP-E, BUB protein kinases

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4
Q

what must occur in spindle assembly checkpoint for anaphase to proceed

A

each BUB protein kinase dissociates from kinetochore when chromosomes are attached to spindle; when all are dissociated, anaphase proceeds

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5
Q

2 roads to aneuploidy regarding spindle assembly checkpoint

A

mis-attachment of microtubules to kinetochores, aberrant centrosome/DNA duplication

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6
Q

4 types of attachments of microtubules to kinetochores

A

syntelic attachment, amphelic attachment, merotelic attachment, monotelic attachment

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7
Q

what is syntelic attachment

A

when the 2 sister kinetochores of an individual chromosome bind microtubules from same spindle pole

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8
Q

what is amphitelic attachment

A

attachment of the 2 sister kinetochores to microtubules from opposite spindle poles (normal attachment)

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9
Q

what is merotelic attachment

A

when a single kinetochore binds microtubules from two poles rather than just one (can break chromosome)

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10
Q

what is monotelic attachment

A

when one of the 2 sister kinetochores of an individual chromosome is attached to one spindle pole whereas the other sister is unattached

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11
Q

examples of how syntelic or merotelic attachments cause aneuploid

A

cohesion defects or syntelic attachments, which cause both sister chromatids to migrate to the same pole, or merotelic attachment, where there is chromosome loss at cytokinesis

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12
Q

what does aberrant centrosome/DNA duplication result in

A

creates 4 centrosomes, misforming and creating multipolar spindles, forming 3 or 4 inviable cells with differing amounts of chromosomes

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13
Q

how can anti-cancer therapy induce gross chromosome mis-segregations to kill tumour cells

A

inhibit attachment-error-correction mechanism, with checkpoint kinase inhibitor binding (cell proceeds to anaphase prematurely), resulting in gross chromosomal mis-segregation and apoptotic cell death

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14
Q

what happens during checkpoint kinase (CHKE1 and CHKE2)

A

serine threonine kinase activation holds cells in G2 phase until all is ready, with inhibition leading to untimely cell transition to mitosis

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15
Q

2 examples of breast and ovarian cancer treatments

A

taxanes and vinca alkaloids

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16
Q

what 3 things do taxanes and vinca alkaloids in treating breast and ovarian cancers

A

alters microtubule dynamics -> produces unattached kinetochores -> causes long-term mitotic arrest

17
Q

3 cell cycle checkpoints, which can be blocked/bypassed by tumours

A

G2 entering M (checking if DNA damage), metaphase checkpoint (exiting from metaphase; ensures sister chromatid alignment), G1 checkpoint (driven by growth factors)

18
Q

which checkpoint are most tumour progressions present

A

G1 checkpoint, as increases speed of cycle (growth factors)

19
Q

where do tumorous cells exit the cell cycle, and what do they do

A

exit cell cycle at G0 (after M) as have no stimulus, but bypass having cell cycle apparatus dismantled so reenter again

20
Q

what happens in G0 (quiescent phase)

A

cells are not dormant, but are non-dividing (carry out function)

21
Q

how do cells exit from G0 phase

A

requires growth factors and IC signalling cascades