p53 contains a DNA break-binding motif similar to the functional part of BRCT-related region of Rb

The BRCT regions are two repeating structures at BRCA1 carboxyl-terminus an d are ubiquitous in some proteins involved in DNA repair and cell cycle che ckpoints. It was shown that BRCTs of TopBP1, BRCA1, and BRCT-Ws of Rb hound DNA ends and breaks. We indicate here that the C-terminus of p53 tumor sup pressor contains a DNA binding motif (residues 327-333 in human), whose fea tures are similar to those of the part of BRCT-W in Rb with DNA binding act ivity. The short motif was required for the gel retardation activity of DNA fragments, since residues 311-333 show cd the activity while residues 311- 326 showed no activity. Significant numbers of total p53 and its fragments with the motif formed multimerizing complexes and associated with DNA ends and breaks, These results suggest the common presence of DNA binding motifs that can recognize DNA ends or damages in major tumor suppressors, Rb, BRC A1 and p53. The oncogenic activity of p53 C-terminus (residues 311-393) req uired both the DNA damage recognition motif and the repair enzyme-associati ng domain. Oncogene (2001) 20, 2859-2867.