p53, the central decision-maker of the DNA damage response
p53 is a tumour suppressor protein (when it is lost, damaged cells keep dividing, which favours cancer) that decides the cell's fate when its DNA is damaged.
Remember
When DNA is damaged, p53 pauses the cell cycle to give time for repair; if the damage cannot be repaired, it triggers apoptosis (programmed cell death) or senescence (permanent exit from the cell cycle).
Memory aid
p53 is the guardian of the genome: it pulls the emergency brake, then decides between repair, retirement (senescence) and shutdown (apoptosis).
p53 pulls the emergency brake, then decides between repair, retirement (senescence) and shutdown (apoptosis).
Cells use checkpoints, points in the cell cycle where division is paused to check that conditions are right and the DNA is intact. These pauses can give time for DNA damage to be repaired, and in healthy cells the checkpoints work to ensure the cell remains healthy and can go through mitosis.
When DNA damage is detected, the protein p53 sits at the centre of the response that follows. If the damage can be repaired, p53 holds the cell in a pause to buy time, and it turns on p21, a protein that blocks the cyclin-dependent kinases (the enzymes that push the cell through the cell cycle). Once the damage is repaired, the cell resumes.
If the damage is too severe to repair, p53 triggers apoptosis (programmed cell death) or senescence (permanent withdrawal from the cell cycle), so that a cell with damaged DNA does not divide.
This is why p53 is called a tumour suppressor. If p53 is lost, damaged cells slip through checkpoints inappropriately and can accumulate more mutations, which is a step towards cancer.
Key facts
- Role
- p53 sits at the centre of the response to DNA damage and decides the cell's fate.
- Often called
- p53 is the guardian of the genome.
- Repairable damage
- p53 holds the cell in a pause in the cell cycle and turns on p21 to buy time.
- What p21 does
- p21 blocks the cyclin-dependent kinases, the enzymes that push the cell through the cell cycle.
- Severe damage
- p53 triggers apoptosis or senescence, so a cell with damaged DNA does not divide.
- If p53 is lost
- Damaged cells pass through checkpoints inappropriately and keep dividing with their mutations, which favours cancer.
Exam traps
- A cyclin-dependent kinase such as CDK1 is not the decision-maker between arrest and apoptosis: it drives the cell forward through the cell cycle, and it is part of the machinery that p53 and p21 hold back.
- An enzyme that builds new DNA strands during replication, such as DNA polymerase delta, copies DNA but does not sense damage or decide the fate of the cell.
- Telomerase reverse transcriptase lengthens the telomeres (the ends of chromosomes) in dividing cells, and it has no role in choosing between arrest and apoptosis.
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