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Research Paper
Facilitated Search for Specific Genomic Targets by p53 C-Terminal Basic DNA Binding Domain
Yuangang Liu, James P. Lagowski, Gretchen E. Vanderbeek and Molly F. Kulesz-Martin
volume 3 | issue 11
november 2004Pages: 1102-1108
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p53 is a unique DNA binding protein with two distinct DNA binding domains, the central domain for sequence-specific DNA binding and the basic DNA binding domain (BD domain) for structure-specific DNA binding. In contrast to the apparent inhibitory effect of the BD domain on p53 binding to sequence-specific DNA in vitro, here we demonstrate that the BD domain enhances p53 binding to the endogenous p21Waf1 promoter and mediates rapid transactivation of p21Waf1. This paradox is resolved by the observation that the BD domain is required for rapid binding to non-sequence-specific genomic DNA (NS-DNA) as evident from global chromatin immunoprecipitation analysis of p53 DNA binding in vivo. This finding provides the first in vivo evidence from a eukaryotic system to support binding to NS-DNA as an intermediate step in searching specific sites as proposed by von Hippel and Berg. Furthermore, we speculate that binding to structure-specific DNA by the BD-domain is a mechanism for p53 rapid binding to genomic DNA from its free state to facilitate the search for its target sites in the genome undergoing genotoxic stress.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.