Cancer Research UK scientists have discovered a missing link in the way cells protect themselves against cancer, according to research published in Genes and Development.
Cancer Research UK-funded scientists based at the University of Dundee and the Agency for Science Technology and Research in Singapore have discovered how cells switch p53, the tumour-suppressor gene known as the guardian of the genome, on and off.
The discovery comes 30 years after the gene was co-discovered by Professor David Lane, who is also Cancer Research UK's chief scientist.
This has important implications for cancer treatment and diagnosis.
The scientists used a genetic trick to make zebrafish turn green when the p53 gene was switched on to explore the way this gene was regulated.
They found that the p53 gene makes the p53 protein and an alternative control-switch variation of the p53 protein, known as an isoform.
It is the isoform that feeds back to regulate the p53 gene.
In its active state, p53 will trigger cell death - called apoptosis - or arrest cell division to make repairs to DNA.
Normally zebrafish can survive low doses of radiation.
But zebrafish that couldn't make this isoform switch died when exposed to low levels of radiation.
This proved the isoform was critical in controlling p53's normal function to protect cells against the development of cancer - which includes ordering cells to die when they are badly damaged.
Scientists from Professor Lane's lab had previously discovered that cells contained more than one isoform of p53 but they didn't know how the isoforms were produced or what they did.
Zebrafish carry the same p53 gene as humans.
P53 is damaged or inactive in half of all cancers and has roles in cell development and ageing.
In normal cells it is activated in response to cell damage and one of its functions is to order cells to die when DNA is damaged beyond repair.
It is critical that p53 functions normally to prevent genetic mistakes being passed on to daughter cells, which can lead to cancer.
But until now no-one understood how this gene was controlled.
Professor Lane said: 'Our research is focused on this p53 gene because it is so often damaged in cancer cells.
'The function of p53 is critical to the way that many cancer treatments kill cells, since radiotherapy and chemotherapy act in part by triggering cell suicide in response to DNA damage.
'So understanding more about how this gene is controlled in cells is really important in finding ways to prevent cells from turning cancerous.'
