Zeroing in on how the ’guardian of the genome’ works

The tumor suppressor protein p53 has been dubbed the 'guardian of the genome' because it protects the DNA from stress or long-term damage by regulating the expression of numerous genes involved DNA repair, cell division and cell death. Now, FMI researchers have homed in on some of the mechanisms that regulate the activation of p53 target genes. By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors. The protein acts as a transcription factor that can be rapidly induced in response to various forms of cellular stress, resulting in immediate activation of genes involved DNA repair, cell division and cell death. Unlike many other transcription factors, p53 can bind closed chromatin — a tightly packed form of DNA and proteins that suppresses gene expression by making the genome inaccessible to transcription factors. But it's unclear how p53 engages closed chromatin and opens it up to activate target genes. Luke Isbel, a postdoctoral fellow in the Schübeler lab , and his colleagues investigated how p53 binds to DNA in mouse embryonic stem cells and human tissues.