The p53 tumor suppressor gene is a critical regulator of normal development involved in cell cycle control pathways, such as growth arrest, differentiation and apoptosis. The DNA binding activity of p53 is central to its function. In addition to the specific DNA binding activity that is confined to the "core" domain of the molecule, the C-terminus seems to play an important role in both controlling the specific as well as exhibiting a non-specific DNA binding activity, which is directly associated with sensing damaged DNA. The C-terminal DNA binding activity appears to be regulated by phosphorylation, glycosylation, splicing and binding of several factors. The C-terminus seems to recognize single and double stranded DNA breaks that occur during DNA replication and recombination, as well as following external DNA stress signals. Unless the cell manages to correct the DNA damage it has the tempting option to progress towards apoptosis. Imagine the C-terminus as a traffic light ensuring the safe "on going" through the cell cycle; in case damaged DNA could not be corrected, p53 dependent apoptosis or terminal differentiation "signs" are turned on!