F lec 19 Flashcards

(42 cards)

1
Q

defined as a delay or arrest in the cell cycle progression in response to problems completing a specific step in the cell cycle or in response to other cellular problems

A

cell cycle checkpoint

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2
Q

cell cycle checkpoints may pause the cell cycle and promote ______________ before continuing - can also induce _____________ ____________ or _______________

A

repair, permanent arrest, apoptosis

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3
Q

cell cycle checkpoints are essential for protecting against _______________

A

cancer

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4
Q

a lot of genes involved in checkpoints are important _______________ ____________________ _____________

A

tumor suppressor genes

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5
Q

the _________ is recruited to unattached kinetochores

A

SAC (spindle assembly checkpoint)

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6
Q

the SAC is recruited to ________________ __________________

A

Unattached kinetochores

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7
Q

the ____________ component of the SAC is what gets recruited to the unattached kinetochore, being activated and then released

A

MAD2

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8
Q

once activated at the kinetochore, Mad2 binds and inhibits ______-_______

A

APC-Cdc20

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9
Q

Mad2 component of the SAC binds and ___________ APC-cdc20 - allows spindle to set up properly before anaphase is initiated

A

inhibits (keeps the APC inactive until the last of the improperly bound chromosomes is properly bound to kinetochore microtubules)

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10
Q

the _____ _________ ______________ _______________ is activated if DNA damage is detected in G1, leading to G1 arrest - this allows the cell cycle to pause while DNA is repaired - there is a similar checkpoint that operates in G2 and prevents entry into mitosis

A

G1 DNA damage checkpoint

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11
Q

checkpoint triggered by telomere shortening - cell replication depends on the enzyme telomerase repairing telomeres, but not all cells have telomerase (only embryos and stem cells) so then the telomeres get shorter and shorter and eventually they get too short to divide, leading to permanent cell cycle arrest

A

replicative senescence (G0)

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12
Q

replicative senescence checkpoints protect against chromosome _______________

A

fusion

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13
Q

2 kinases that are recruited to sites of DNA damage

A

ATR, ATM

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14
Q

kinase that is recruited to double strand DNA breaks

A

ATM

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15
Q

kinase that is recruited to exposed single stranded DNA and other DNA damage (including stalled replication fork since there is exposed ssDNA there as well)

A

ATR

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16
Q

DNA damage checkpoints:

A

chk1, chk2

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17
Q

2 functions of ATM and ATR when recruited to sites of DNA damage

A

helps recruit repair machinery, activates a cell cycle checkpoint

18
Q

DNA damage checkpoints:

A

reversible cell cycle arrest

19
Q

once bound to its cyclin partner, a CDK still needs activating phosphorylation from a ________

20
Q

enzyme that phosphorylates CDK1 to inhibit its activity

21
Q

__________ ____________________ removes the inhibitory phosphate placed on CDK1 by Wee1 kinase

A

cdc25 phosphatase

22
Q

_________ ______________ is necessary to activate CDK1 and CDK2 because it removes the inhibitory phosphate

A

cdc25 phosphatase

23
Q

phosphorylation of cdc25 by chk1 and chk2 leads to its ___________________

24
Q

phosphorylation of cdc25 by chks (which degrades it) and by cdks (which activates it) seems contradictory, but still can be so because the phosphorylations are occurring at ______ _______________ ____________ of the cdc25 protein

A

2 different sites

25
when cdc25 phosphatase is degraded, the inhibitory phosphate on CDK cannot be removed and so therefore the CDK is ________________ and _____ ___________ occurs
inactivated, G1 arrest
26
DNA damage checkpoint:
JUST READ IT
27
cell cycle arrest or apoptosis occurring when DNA damage is too severe depends on the activation of an important protein called ________
p53
28
ATM, ATR, Chk1, and Chk2 can all phosphorylate p53, which causes it to become ____________
active
29
p53 (when active) is a transcription factor and its primary target is _______, which is a CDK inhibitor
p21 ( binds and inhibits CDK2 complexes)
30
when p53 becomes activated when there is cell damage, it will act as a transcriptional activator for p21, which will inhibit CDK2 complexes and the cell will fail to enter ____-______________ = permanent cell cycle arrest usually
S-phase
31
p53 can also induce ________________ when things are really bad by activating the expression of ____________________ _____________
apoptosis, pro-apoptotic genes
32
p53 activity is normally kept controlled at low levels when the cells are not extensively damaged, which is primarily the responsibility of its inhibitor called _________, which binds to p53 to inhibit it
mdm2
33
mdm2 not only binds to p53 to inhibit it, but it also _______________ p53, leading to its destruction by a proteasome
ubiquitinates
34
___________________ of p53 is what relieves its inhibition by mdm2, allowing it to be released from mdm2 and trigger cell cycle arrest in damaged cells by activating the transcription of p21 = cells that arrest in G1
phosphorylation (by Chk1/Chk2 and ATM/ATR)
35
phosphorylation of p53 is what relieves its inhibition by mdm2, allowing it to be released from mdm2 and trigger cell cycle arrest in damaged cells by activating the transcription of p21 = cells that arrest in _______
G1
36
the cdc25 DNA damage checkpoint is regarded more as a ________________ stop of the cell cycle
transient
37
the p53 DNA damage checkpoint is activated when damage is more extensive and is regarded as a ________________ arrest
permanent
38
only cells that have active telomerase
embryonic cells, stem cells
39
telomeres are protected by a _____________ __________ that protects telomeres from DNA machinery that recognizes ds breaks - without this there will appear to be many ds breaks in the DNA at telomeres
sheltrin complex
40
the binding of the sheltrin complex protects telomeres from DNA repair machinery that repairs _____________ ______________ ______________
double stranded breaks (ATM protein recruited)
41
______________ binds to the repeats of the telomere, but if the telomeres shorten too much then there are no repeat sequences and it cannot bind any more
sheltrin
42
when sheltrin complex can no longer bind to the telomere repeats since they've become too short, the ds break sensing checkpoint recognizes the ends of these chromosomes and induces permanent cell cycle arrest through the p53 pathway called ______________ ________________
replicative senescence (SLIDE 18)