Nucleic Acids Research, Vol 24, Issue 18 3560-3567, Copyright © 1996 by Oxford University Press
G Selivanova, V Iotsova, E Kiseleva, M Strom, G Bakalkin, RC Grafstrom and KG Wiman
p53 is a transcription factor that binds double-stranded (ds) DNA in a
sequence-specific manner. In addition, p53 can bind the ends of single-
stranded (ss) DNA. We previously demonstrated that ssDNA oligonucleotides
interact with the C-terminal domain of p53 and stimulate binding to
internal segments of long ssDNA by the p53 core domain. Here we show that
the p53 C-terminal domain can recognize staggered ss ends of dsDNA. We have
mapped the binding site for ssDNA ends to residues 361-382 in human p53
using a p53 deletion mutant (p53- delta 30) lacking the 30 C-terminal amino
acid residues and a series of 22mer peptides. The binding site for DNA ends
coincides with a region previously implicated in regulation of
sequence-specific DNA binding by the core domain. The interaction of the
C-terminal regulatory domain with the ends of ssDNA or with the protruding
ends of dsDNA stimulates both sequence-specific and non-specific DNA
binding via the core domain. Electron microscopy demonstrated the
simultaneous binding of p53 to dsDNA and a ssDNA end. These results suggest
a model in which interaction of the p53 C-terminal tail with DNA ends
generated after DNA damage causes activation of sequence-specific p53 DNA
binding in vivo and may thus provide a molecular link between DNA damage
and p53- mediated growth arrest and apoptosis.
ARTICLES
The single-stranded DNA end binding site of p53 coincides with the C- terminal regulatory region
Department of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
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