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Cancer Biology > Cell Cycle Dysregulation > Flashcards

Cell Cycle Dysregulation Flashcards

1
Q

the cell cycle clock operates in the

A

cells’ nucleus

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2
Q

the cell cycle clock processes..

A

incoming signals both from inside and outside the cell

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3
Q

the cell cycle clock decides on

A

-entering active cell cycle
-retreating into nonproliferating state

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4
Q

what are known as the cell cycle regulators

A

promoting & inhibiting factors

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5
Q

what is known as the S phase promoting factor

A

cyclin A/ CDK2

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6
Q

what is known as the maturation promoting factor

A

cyclin B/ CDC25B

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7
Q

which inhibitory factor inhibits CDK4/6

A

P16INK4

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8
Q

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

A

P27KIP1

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9
Q

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

A

cyclins
Cdks

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10
Q

what controls the different stages of the cell cycle

A

different cyclin/Cdk complexes

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11
Q

cyclin B forms complexes that…

A

allow entrance into M phase

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12
Q

cyclin E increases..

A

after passing R point

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13
Q

cyclin A increases…

A

with cells entrance into S phase

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14
Q

what are the 4 different checkpoints for DNA damage

A
  1. spindle assembly checkpoint
  2. G1 checkpoint
  3. S checkpoint
  4. G2 checkpoint
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15
Q

the spindle assembly checkpoint checks for…

A
  • chromosome attachment to spindle
  • chromosome alignment
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16
Q

the G1 checkpoint checks for…

A
  • cell size
  • nutrients
  • GF
  • DNA damage
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17
Q

the S checkpoint checks for…

A
  • only 1 DNA replication
  • DNA damage
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18
Q

the G2 checkpoint checks for…

A
  • cell size
  • DNA replication
  • DNA damage
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19
Q

the spindle assembly checkpoint occurs during the

A

M phase

20
Q

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

A

transient cycle arrest

21
Q

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

A
  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)
22
Q

what licensing factor can only bind in G1

A

MCM helicase

23
Q

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

A
  • rereplication of previously replicated DNA
  • cells gain or lose chromosomes
  • DNA damage goes undetected
24
Q

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

A

Rad17

25
Q

the absence of what protein causes improper alignment during metaphase

A

Bub1
- normally prevents separation of chromosomes if not aligned properly

26
Q

cells that lack _____ have fragile sites in the chromosomes

A

ATR protein kinase

27
Q

what is the function of ATR protein kinase?

A

stopping DNA replication until replication forks are repaired

28
Q

explain the steps in cdk/cyclin regulation

A
  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
29
Q

Cdk/cyclin regulation is through

A

double phosphorylation by kinases and dephosphorylation by phosphatases

30
Q

wild type p53…

A

suppresses cell proliferation

31
Q

what causes p53 to become growth promoting

A

a point mutation in the reading frame

32
Q

sensor proteins recognize damaged DNA and activate…

A

ATM

33
Q

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

A

p21 inhibits Cdk-cyclin complex leading to cell cycle arrest

34
Q

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

A

b/c Cdk-cyclin can NOT phosphorylate Rb protein

35
Q

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

A

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

36
Q

list 6 factors that cause p53 levels to rise

A
  1. lack of nucleotides
  2. UV radiation
  3. ionizing radiation
  4. oncogene signaling
  5. hypoxia
  6. blockage of transcription
37
Q

after p52 levels rise p53 undergoes..

A

post-translational modifications

38
Q

post-translational modifications in p53 lead to what 4 responses

A
  1. cell cycle arrest
  2. DNA repair
  3. angiogenesis blocked
  4. apoptosis
39
Q

what is the most commonly mutated gene in human cancers?

A

p53

40
Q

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

A

those missing both alleles (homozygotes)

41
Q

what does APC stand for

A

anaphase promoting complex

42
Q

APC’s function

A

triggers anaphase

43
Q

how does APC trigger anaphase

A

by activating enzymes that degrade cohesins

44
Q

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

A

spindle checkpoint

45
Q

what is the “wait” signal that chromosomes send when they’re not properly attached to the spindles

A

Mad-Bub

46
Q

how does Mad-Bub function as a ‘wait’ signal?

A

by inhibiting Cdc20 which is need for chromosome separation

47
Q

function of Cdc20

A

activates separase enzyme

Cancer Biology (15 decks)

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