DNA Damage And Cell Cycle Checkpoints Flashcards

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1
Q

What are cell cycle checkpoints

A

Points where the cell checks if chromosomes are proper before moving one to the next step in the cycle

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2
Q

What happens if cells override the cell cycle checkpoints and there is still dna damage

A

Cancerous mutations

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3
Q

What are the 6 sources of every day dna damage

A

Uv from sun

Chemical carcinogens

Replication induced damage (due to replication)

X rays

Gamma rays

Radon gas

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4
Q

What are the potential ways to responding to dna damage

A
  1. Repair of the damage
  2. Activation of the dna damage checkpoint (to stop the cell cycle for repair)
  3. Or apoptosis (programmed cell death)
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5
Q

How does cancer come about

A

Due to unrepaired or poorly repaired dna damage

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6
Q

What are the causes of cell cycle arrest

A

The chromosomal dna is damaged

Critical events in the cycle are incomplete

Replication in S phase is incomplete

Alightment of chromosomes in M phase is improper

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7
Q

What is AT

What is ATM

A

An inherited recessive disorder

makes people sensitive to ionizing radiation, the gene encodes a protein kinase

AT-mutated, a kinase that is recruited when a double strand break happens in the dna

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8
Q

What is ATR

A

A protein kinase that is activated by dna damage from uv light

The damage is a single stranded dna break due to uv light

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9
Q

What 3 things can arrest the progression though the cell cycle at a checkpoint

A

Sensors

Transmitters/transducers

Effectors

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10
Q

What is a sensor

Give example

A

Detect chromosomal abnormalities (DNA damage)

ATM AND ATR

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11
Q

What are transmitters/transducers

A

They signal the information

Checkpoint kinases: CHK1 CHK2

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12
Q

What are effectors

Give example

A

Inhibit cell cycle machinery

p53 (guardian of the genome, tumor suppressor)

CDC25 (phosphatase that removes the WEE1 phosphate)

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13
Q

What does ATM protien kinase activate

And how is it activated

A

Activates CHK2 by phosphorylating it

Activated by ionizing radiation induced double strand breaks

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14
Q

What does ATR protien kinase activate

And how is it activated

A

Activates CHK1 by phosphorylating it

Activated by uv radiation induced single stranded breaks

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15
Q

What are the two dna damage checkpoints

A

The G2/M

G1-S

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16
Q

What checkpoint does ATM control

A

G1-S

17
Q

What checkpoint does ATR control

A

G2/M

18
Q

What is the G2/M Checkpoint

A

Stops cells from going to M phase when there is dna damage

19
Q

Describe how ATR carried out the G2/M checkpoint arrest when there damage

A

Single stranded break due to uv

ATR phosphorylates CHK1 to activate it

CHK1phosphorylates the phosphatase cdc25 which moves cdc25 out of the cell and inactivated it

cdc25 inactivation caused cell cycle arrest because it can’t remove the tyr15 phosphate on the CDK

20
Q

Where is the g1/S checkpoint

A

Between g1 and s phase

21
Q

Describe how ATM carries out cell cycle arrest

A

Double strand break due to ionizing radiation activated ATM

ATM phosphorylates CHK2 and activated it

The active CHK2 stablizes p53 by phosphorylating it

Stable p53 transcribes p21 which inhibits the cdk

Cell cycle arrest

22
Q

What is p21 and what does it do

A

It’s an inhibitor of the G1 cdk when the dna is damaged at the g1/s checkpoint

This makes it so the pRB is not phosphorylated since kinase is inhibited (need to be phosphorylated to let cell cycle continue)

23
Q

Other than p21 what can p53 also transcribe

What does this do

A

Can transcribe cell death protiens

If repair isnt possible it help with cell death

24
Q

Describe how pRB represses genes at g1/s ohase

A

In g1 E2F is bound to pRB on the promoter region of the dna

This is a repressive effect

When a cdk is active, it phosphorylates pRB and releases from E2F

This makes E2F an activator and the cell cycle cintinues

25
Q

What does pRB being phosphorylated do

A

Inhibits pRB, makes it fall off, and activates cell cycle

26
Q

ATM and ATR share responsibility for which checkpoints

A

All except m phase

27
Q

Is p21 a kinase

A

No