F lec 19

Question 1

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

Answer 1

cell cycle checkpoint

Question 2

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

Answer 2

repair, permanent arrest, apoptosis

Question 3

cell cycle checkpoints are essential for protecting against _______________

Answer 3

cancer

Question 4

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

Answer 4

tumor suppressor genes

Question 5

the _________ is recruited to unattached kinetochores

Answer 5

SAC (spindle assembly checkpoint)

Question 6

the SAC is recruited to ________________ __________________

Answer 6

Unattached kinetochores

Question 7

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

Answer 7

MAD2

Question 8

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

Answer 8

APC-Cdc20

Question 9

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

Answer 9

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

Question 10

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

Answer 10

G1 DNA damage checkpoint

Question 11

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

Answer 11

replicative senescence (G0)

Question 12

replicative senescence checkpoints protect against chromosome _______________

Answer 12

fusion

Question 13

2 kinases that are recruited to sites of DNA damage

Answer 13

ATR, ATM

Question 14

kinase that is recruited to double strand DNA breaks

Answer 14

ATM

Question 15

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)

Answer 15

ATR

Question 16

DNA damage checkpoints:

Answer 16

chk1, chk2

Question 17

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

Answer 17

helps recruit repair machinery, activates a cell cycle checkpoint

Question 18

DNA damage checkpoints:

Answer 18

reversible cell cycle arrest

Question 19

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

Answer 19

CAK

Question 20

enzyme that phosphorylates CDK1 to inhibit its activity

Answer 20

Wee1 kinase

Question 21

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

Answer 21

cdc25 phosphatase

Question 22

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

Answer 22

cdc25 phosphatase

Question 23

phosphorylation of cdc25 by chk1 and chk2 leads to its ___________________

Answer 23

degradation

Question 24

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

Answer 24

2 different sites

Question 25

when cdc25 phosphatase is degraded, the inhibitory phosphate on CDK cannot be removed and so therefore the CDK is ________________ and _____ ___________ occurs

Answer 25

inactivated, G1 arrest

Question 26

DNA damage checkpoint:

Answer 26

JUST READ IT

Question 27

cell cycle arrest or apoptosis occurring when DNA damage is too severe depends on the activation of an important protein called ________

Answer 27

p53

Question 28

ATM, ATR, Chk1, and Chk2 can all phosphorylate p53, which causes it to become ____________

Answer 28

active

Question 29

p53 (when active) is a transcription factor and its primary target is _______, which is a CDK inhibitor

Answer 29

p21 ( binds and inhibits CDK2 complexes)

Question 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

Answer 30

S-phase

Question 31

p53 can also induce ________________ when things are really bad by activating the expression of ____________________ _____________

Answer 31

apoptosis, pro-apoptotic genes

Question 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

Answer 32

mdm2

Question 33

mdm2 not only binds to p53 to inhibit it, but it also _______________ p53, leading to its destruction by a proteasome

Answer 33

ubiquitinates

Question 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

Answer 34

phosphorylation (by Chk1/Chk2 and ATM/ATR)

Question 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 _______

Answer 35

G1

Question 36

the cdc25 DNA damage checkpoint is regarded more as a ________________ stop of the cell cycle

Answer 36

transient

Question 37

the p53 DNA damage checkpoint is activated when damage is more extensive and is regarded as a ________________ arrest

Answer 37

permanent

Question 38

only cells that have active telomerase

Answer 38

embryonic cells, stem cells

Question 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

Answer 39

sheltrin complex

Question 40

the binding of the sheltrin complex protects telomeres from DNA repair machinery that repairs _____________ ______________ ______________

Answer 40

double stranded breaks (ATM protein recruited)

Question 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

Answer 41

sheltrin

Question 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 ______________ ________________

Answer 42

replicative senescence (SLIDE 18)