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 and are ubiquitous in some proteins involved in DNA repair and cell cycle checkpoints. It was shown that BRCTs of TopBP1, BRCA1, and BRCT-Ws of Rb bound DNA ends and breaks. We indicate here that the C-terminus of p53 tumor suppressor contains a DNA binding motif (residues 327-333 in human), whose features are similar to those of the part of BRCT-W in Rb with DNA binding activity. The short motif was required for the gel retardation activity of DNA fragments, since residues 311-333 showed 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, BRCA1 and p53. The oncogenic activity of p53 C-terminus (residues 311-393) required both the DNA damage recognition motif and the repair enzyme-associating domain.
Yamane
K
K
Laboratory of Biomedical Research, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Katayama
E
E
Tsuruo
T
T
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019313:BRCA1 Protein / Q000378:metabolism; D001665:Binding Sites; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D015951:Factor Xa / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D016160:Retinoblastoma Protein / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D019313:BRCA1 Protein; D004277:DNA, Single-Stranded; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D015951:Factor Xa