Shemanko lecture 12 Flashcards
If cells go through cell cycle checkpoints with existing DNA damage what happens?
Could lead to cancerous mutations if 5-7 mutations are present
What are 6 sources of DNA damage in everyday life?
UV exposure from the sun
Chemical carcinogens
Replication induced damage
X rays
Gamma rays
Radon gas
What are the three DNA damage response actions?
- Repair of DNA damage
- activation of a DNA damage checkpoint and arrest of the cell cycle for repair
- If no repair, apoptosis- programmed cell death
Cancer is a consequence of what?
Unrepaired or poorly repaired DNA damage
What are the cell cycle checkpoints, ie what halts the cell cycle of this happens?
If chromosomal dna is damaged
if critical events incomplete such as DNA replication in S phase or chromosomal alignment during M phase
What is Ataxia-telangiectasia? What does it do in response to double-strand dna breaks?
Is an inherited recessive disorder, encodes a protein kinase called ATM-AT mutated which is activated by double-strand DNA breaks
What protein kinase is activated by single-strand DNA breaks?
protein kinase ATR, activated by UV induced DNA damage
What two checkpoints are in the mammalian cell cycle?
pRB dephosphorylation, between G2 and M phase and prb phosphorylation at end of G1 phase.
What 3 things arrests progress through the cell cycle?
- Sensors that detect chromosomal abnormalities
- ATM
-ATR - Transmitters/transducers that signal the information
-CHK1
-CHK2 - Effectors that inhibit cell cycle machinery
-p53
-cdc25
What does ATM activate?
CHK2
What does ATR activate?
CHK1
ATM caused by what type of radiation?
ionizing
ATR caused by what type of radiation?
UV
How is DNA damage prevented at the G2/M checkpoint by ATR?
ATR activates CHK1 through phosphorylation, this then phosphorylates cdc25, which inactivates it which causes the G2/M phase to be at arrest
How does ATM arrest the cell cycle at the G1/S checkpoint?
Double strand DNA break leads to ATM activation and Chk2 gets phosphorylated and becomes active, this makes p53 stable which transcribes the p21 protein, the p21 protein inhibits the G1 cdk, so no prb is phosphorylated and therefore nothing gets transcribed and we don’t get into S phase.
