DNA Damage And Cell Cycle Checkpoints Flashcards
What are cell cycle checkpoints
Points where the cell checks if chromosomes are proper before moving one to the next step in the cycle
What happens if cells override the cell cycle checkpoints and there is still dna damage
Cancerous mutations
What are the 6 sources of every day dna damage
Uv from sun
Chemical carcinogens
Replication induced damage (due to replication)
X rays
Gamma rays
Radon gas
What are the potential ways to responding to dna damage
- Repair of the damage
- Activation of the dna damage checkpoint (to stop the cell cycle for repair)
- Or apoptosis (programmed cell death)
How does cancer come about
Due to unrepaired or poorly repaired dna damage
What are the causes of cell cycle arrest
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
What is AT
What is ATM
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
What is ATR
A protein kinase that is activated by dna damage from uv light
The damage is a single stranded dna break due to uv light
What 3 things can arrest the progression though the cell cycle at a checkpoint
Sensors
Transmitters/transducers
Effectors
What is a sensor
Give example
Detect chromosomal abnormalities (DNA damage)
ATM AND ATR
What are transmitters/transducers
They signal the information
Checkpoint kinases: CHK1 CHK2
What are effectors
Give example
Inhibit cell cycle machinery
p53 (guardian of the genome, tumor suppressor)
CDC25 (phosphatase that removes the WEE1 phosphate)
What does ATM protien kinase activate
And how is it activated
Activates CHK2 by phosphorylating it
Activated by ionizing radiation induced double strand breaks
What does ATR protien kinase activate
And how is it activated
Activates CHK1 by phosphorylating it
Activated by uv radiation induced single stranded breaks
What are the two dna damage checkpoints
The G2/M
G1-S