Tumour suppressor genes are normal genes that slow down cell division. Their proteins stop the cell cycle when necessary, help repair damaged DNA, and trigger apoptosis (programmed cell death) in cells whose DNA is too damaged to repair. An example is the gene for the protein p53, which stops the cell cycle when DNA is damaged. Others are BRCA1 and BRCA2, whose proteins help repair DNA.If a tumour suppressor gene is inactivated, its protein is not made or does not work. Cell division is no longer slowed, damaged cells are neither repaired nor destroyed, and cells divide uncontrollably, forming a tumour. A tumour suppressor gene can be inactivated by:
• a mutation in its base sequence, so a non-functional protein, or no protein, is made
• hypermethylation (increased methylation) of its promoter, which silences it without changing the base sequence.Cells have two alleles of each tumour suppressor gene. Usually both alleles must be inactivated before control is lost, because one working allele makes enough protein. A person who inherits one faulty allele, such as a faulty BRCA1 allele, needs only one further change in a cell, so they have a much higher risk of cancer.Compare this with oncogenes (next lesson): tumour suppressor genes cause cancer when they are switched off, whereas oncogenes cause cancer when they are switched on. Most tumours develop only after several such changes build up in the same cell line.
• a mutation in its base sequence, so a non-functional protein, or no protein, is made
• hypermethylation (increased methylation) of its promoter, which silences it without changing the base sequence.Cells have two alleles of each tumour suppressor gene. Usually both alleles must be inactivated before control is lost, because one working allele makes enough protein. A person who inherits one faulty allele, such as a faulty BRCA1 allele, needs only one further change in a cell, so they have a much higher risk of cancer.Compare this with oncogenes (next lesson): tumour suppressor genes cause cancer when they are switched off, whereas oncogenes cause cancer when they are switched on. Most tumours develop only after several such changes build up in the same cell line.