Cell Cycle Dysregulation

Question 1

the cell cycle clock operates in the

Answer 1

cells’ nucleus

Question 2

the cell cycle clock processes..

Answer 2

incoming signals both from inside and outside the cell

Question 3

the cell cycle clock decides on

Answer 3

-entering active cell cycle
-retreating into nonproliferating state

Question 4

what are known as the cell cycle regulators

Answer 4

promoting & inhibiting factors

Question 5

what is known as the S phase promoting factor

Answer 5

cyclin A/ CDK2

Question 6

what is known as the maturation promoting factor

Answer 6

cyclin B/ CDC25B

Question 7

which inhibitory factor inhibits CDK4/6

Answer 7

P16INK4

Question 8

which inhibitory factor…
makes sure damaged DNA is NOT copied
blocks advancement into R point
stimulates formation of cyclin D/ CDK4,6 complex
is found in high conc. when the cell is in G0

Answer 8

P27KIP1

Question 9

Growth factors stimulate the cell to produce _____ which bind _____.

Answer 9

cyclins
Cdks

Question 10

what controls the different stages of the cell cycle

Answer 10

different cyclin/Cdk complexes

Question 11

cyclin B forms complexes that…

Answer 11

allow entrance into M phase

Question 12

cyclin E increases..

Answer 12

after passing R point

Question 13

cyclin A increases…

Answer 13

with cells entrance into S phase

Question 14

what are the 4 different checkpoints for DNA damage

Answer 14

1. spindle assembly checkpoint
2. G1 checkpoint
3. S checkpoint
4. G2 checkpoint

Question 15

the spindle assembly checkpoint checks for…

Answer 15

• chromosome attachment to spindle
• chromosome alignment

Question 16

the G1 checkpoint checks for…

Answer 16

• cell size
• nutrients
• GF
• DNA damage

Question 17

the S checkpoint checks for…

Answer 17

• only 1 DNA replication
• DNA damage

Question 18

the G2 checkpoint checks for…

Answer 18

• cell size
• DNA replication
• DNA damage

Question 19

the spindle assembly checkpoint occurs during the

Answer 19

M phase

Question 20

what results from any DNA damage that is detected by cell cycle checkpoints?

Answer 20

transient cycle arrest

Question 21

what are the steps needed to surpass the restriction point of the cell cycle?

Answer 21

1. GF bind to receptor producing active Cdk-cyclin
2. Cdk-cyclin adds phosphate group to Rb protein
3. Rb can NOT exert inhibitory influence -> E2F is released
4. cells move into S phase (transcription)

Question 22

what licensing factor can only bind in G1

Answer 22

MCM helicase

Question 23

what are 3 consequences of losing control of cell cycle checkpoints?

Answer 23

• rereplication of previously replicated DNA
• cells gain or lose chromosomes
• DNA damage goes undetected

Question 24

the loss of what checkpoint gene leads to the re-replication of DNA?

Answer 24

Rad17

Question 25

the absence of what protein causes improper alignment during metaphase

Answer 25

Bub1 - normally prevents separation of chromosomes if not aligned properly

Question 26

cells that lack _____ have fragile sites in the chromosomes

Answer 26

ATR protein kinase

Question 27

what is the function of ATR protein kinase?

Answer 27

stopping DNA replication until replication forks are repaired

Question 28

explain the steps in cdk/cyclin regulation

Answer 28

1. mitotic Cdk and mitotic cyclin bind forming an inactive complex 2. inhibiting kinases attach 2 inhibitory phosphate groups to the Cdk molecule 3. activating kinases add an activating phosphate group 4. phosphatase removes the inhibiting phosphate groups activating the Cdk-cyclin complex

Question 29

Cdk/cyclin regulation is through

Answer 29

double phosphorylation by kinases and dephosphorylation by phosphatases

Question 30

wild type p53...

Answer 30

suppresses cell proliferation

Question 31

what causes p53 to become growth promoting

Answer 31

a point mutation in the reading frame

Question 32

sensor proteins recognize damaged DNA and activate...

Answer 32

ATM

Question 33

what role of p53 in response to DNA damage leads to cell cycle arrest

Answer 33

p21 inhibits Cdk-cyclin complex leading to cell cycle arrest

Question 34

during the role of p53 in response to DNA damage why can Cdk-cyclin not activate mitosis

Answer 34

b/c Cdk-cyclin can NOT phosphorylate Rb protein

Question 35

what role of p53 in response to DNA damage leads to apoptosis

Answer 35

puma is activated binding to Bcl2 relieving its inhibition on proapoptotic Bax

Question 36

list 6 factors that cause p53 levels to rise

Answer 36

1. lack of nucleotides 2. UV radiation 3. ionizing radiation 4. oncogene signaling 5. hypoxia 6. blockage of transcription

Question 37

after p52 levels rise p53 undergoes..

Answer 37

post-translational modifications

Question 38

post-translational modifications in p53 lead to what 4 responses

Answer 38

1. cell cycle arrest 2. DNA repair 3. angiogenesis blocked 4. apoptosis

Question 39

what is the most commonly mutated gene in human cancers?

Answer 39

p53

Question 40

which mutations in mouse germ line alleles resulted in succumbing to malignancies by day 250?

Answer 40

those missing both alleles (homozygotes)

Question 41

what does APC stand for

Answer 41

anaphase promoting complex

Question 42

APC's function

Answer 42

triggers anaphase

Question 43

how does APC trigger anaphase

Answer 43

by activating enzymes that degrade cohesins

Question 44

what checkpoint delays anaphase until chromosomes have been attached to the spindles?

Answer 44

spindle checkpoint

Question 45

what is the "wait" signal that chromosomes send when they're not properly attached to the spindles

Answer 45

Mad-Bub

Question 46

how does Mad-Bub function as a 'wait' signal?

Answer 46

by inhibiting Cdc20 which is need for chromosome separation

Question 47

function of Cdc20

Answer 47

activates separase enzyme