Phys Conc 6 - Cell Cycle Flashcards

1
Q

what is the cell cycle?

A

the orderly sequence of events by which a cell duplicates its contents and divides in 2

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2
Q

what are the 2 main phases of the cell cycle

A

mitotic phase and interphase

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3
Q

what are the subphases of interphase

A
  • G1 phase
  • S phase
  • G2 phase
  • G0 phase
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4
Q

what is the G1 phase?

A

first gap phase
- preparatory growth phase prior to cell entering DNA synthesis phase
- cell is metabolically active
- many organelles are duplicated but no DNA replication
- 6-24 hours

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5
Q

what is the S phase?

A

DNA and chromosomal protein synthesis occurs
7-8 hours
cell is NOT committed to cell division
- DNA replication occurs here

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6
Q

what is the G2 phase?

A

Second growth phase
- interval between DNA synthesis (S phase) and mitosis (M phase)
- enzyme, protein, and ATP synthesis occurs here

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7
Q

what is the M phase?

A

mitotic phase
- cell undergoes mitosis and then cytokinesis
1-2 hours

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8
Q

what is the G0 phase

A

state of withdrawal from cell cycle
- cell is neither dividing nor preparing to divide
the cell is “doing its job”

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9
Q

what are the features of the cell cycle control system?

A
  1. generally binary (on/off) to launch an event in complete and irreversible fashion
  2. robust and reliable - contains back up mechanisms
    - adaptable and modified to suit specific cell types
  3. adaptable and modified to suit specific cell types
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10
Q

what are checkpoints (transitions)

A

points in the cell division cycle where progress through the cycle can be halted until conditions are suitable for the cell to proceed to the next stage

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11
Q

what are the 3 main regulatory transitions?

A
  1. start transition (G1/S)
  2. G2/M transition
  3. metaphase to anaphase transition ( M to A)
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12
Q

what is the rate limiting and committing step of the cell cycle?

A

G1/S checkpoint

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13
Q

what are cyclin dependent kinases? (cdks)

A

there are enzymes that are responsible for cyclical changes in phosphorylation of intracellular proteins that initiate/regulate the major events of the cell cycle

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14
Q

cdks are controlled by a group of proteins called ?

A

cyclins

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15
Q

what is needed to progress through a checkpoint?

A

cyclin-cdk complexes
(except M-A checkpoint)

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16
Q

what are the 4 classes of cyclins we need to know?

A
  • cyclin D
  • cyclin E
  • Cyclin A
  • Cyclin B
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17
Q

what is the G1 cyclin and what complex does it form with

A

cyclin D forms complex with Cdk 4 or Cdk6
- needed for initiation of transcription of G1/S cyclins

18
Q

what is the G1/S cyclin and what complex does it form with?

A

Cyclin E forms complex with Cdk2 and helps trigger progression through start transition

19
Q

what is the S-cyclin and what complex does it form with?

A

Cyclin A forms complex with cdk1 and cdk2
- helps stimulate chromosome duplication during S phase

20
Q

what is the M cyclin and what complex does it form with?

A

Cyclin B forms complex with cdk1 and it stimulate entry into mitosis at the G2/M transition

21
Q

other than simply activating the cdk what else does the cyclin do?

A

directs it to a specific target protein

22
Q

explain the metaphase-to-anaphase checkpoint

A

occurs via regulated protelysis
need APC/C (anaphase promoting complex) and it polyubiquitinates specific target proteins for destruction in proteasomes

23
Q

what happens at the G1/S checkpoint

A

active G1-cdk and G1/S-cdk complexes will target a protein called RB and phosphorylate it
Inactive RB then releases a transcription factor E2F allowing transcription to proceed

24
Q

what is RB

A

a transcription co-repressor specifically E2F

25
Q

what does the APC/C complex target?

A

securin which is an inhibitory protein that protects protein linkages that hold sister-chromatid pairs together in early mitosis

26
Q

the order of mitosis

A

prophase -> pro-metaphase -> metaphase -> M-to-A checkpoint -> anaphase -> telophase -> cytokinesis

27
Q

progression through G1 is delayed if:

A
  • DNA is damaged by radiation, chemicals, or errors
  • absence of nutrients or growth factors
  • abnormal cell size
28
Q

entry into M is prevented when:

A
  • DNA replication is not complete
  • presence of DNA damage
  • Abnormal cell size
29
Q

progression through M-to-A is prevented if

A

chromosomes are not properly attached to mitotic spindle

30
Q

what are CKIs?

A

Cdk inhibitory proteins which inactivates cyclin-cdk complexes by binding stimulate rearrangement in structure of the cdk active site

31
Q

what are the 3 important CKIs?

A

p16, p21, p27

32
Q

what does p16 inhibits?

A

cyclin D-cdk4 and CyclinD-cdk5 (G1-cdk complex)

33
Q

what does p21 inhibits?

A
  • cyclin E-cdk2 (G1/S-cdk complex
  • cyclin A-cdk2 and cyclin A-cdk1 (S-cdk complex)
  • cyclin B-cdk1 (M-cdk complex)
34
Q

what does p27 inhibits?

A
  • cyclin A-cdk2 and cyclin A-cdk1 (S-cdk complex)
  • cyclin E-cdk2 (G1/S-cdk complex)
  • cyclin B-cdk1 (M-cdk complex)
35
Q

what is P53?

A

a tumour suppressor genes
- recognizes and binds damaged DNA

36
Q

what is the protein that degrades p53 when not needed

A

Mdm2

37
Q

explain the process of p53 and DNA damage

A
  • In the presence of DNA damage, p53 will be phosphorylated, releasing Mdm2
  • P53 will not be degraded
  • Active p53 binds DNA and promotes the transcription of p21
  • P21 binds the G1/S-cdk complex inhibiting it
    An inactive G1/S-cdk complex will pause the cell cycle at the G1/S transition
38
Q

explain the process of RB and DNA damage

A
  • In the presence of a growth suppressor signal or DNA damage
    • P16 is transcribed; p16 inhibits the G1-cdk complex, which was needed to inactivate RB
    • RB remains activated and bound to E2F
      § No transcription of G1/S-cyclins or S-cyclins
      § Cell cycle is paused at start transition
39
Q

what is contact inhibition

A

the cell cycle progression can also be inhibited due to contact with other cells or a basement membrane

40
Q

how does Akt promote cell cycle progression?

A
  • Akt activates/increases:
    § Cyclin A -> activation of CDK-1
    § Cyclin D -> activation of CDK-4/6
  • Akt decreases/inactivates:
    § P21 and p27