Published online 18 February 2005
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Mutant p53 proteins bind DNA in a DNA structure-selective mode
1 Department of Tumor Virology, Heinrich-Pette-Institute Martinistrasse 52, 20251 Hamburg, Germany 2 Evotec OAI Schnackenburgallee 114, 22525 Hamburg, Germany 3 School of Life Science, Tokyo University of Pharmacy and Life Science Horinouchi, Hachioji, Tokyo 192-0392, Japan 4 Neuro-Oncology Group, Department of Neurosurgery, University of Schleswig-Holstein Campus Luebeck, Ratzeburger Allee 160, 23583 Luebeck, Germany
*To whom correspondence should be addressed. Tel: +49 (0)4048051 261; Fax: +49 (0)4048051 117; Email: wolfgang.deppert{at}hpi.uni-hamburg.de
Received September 30, 2004. Revised January 4, 2005. Accepted January 27, 2005.
Despite the loss of sequence-specific DNA binding, mutant p53 (mutp53) proteins can induce or repress transcription of mutp53-specific target genes. To date, the molecular basis for transcriptional modulation by mutp53 is not understood, but increasing evidence points to the possibility that specific interactions of mutp53 with DNA play an important role. So far, the lack of a common denominator for mutp53 DNA binding, i.e. the existence of common sequence elements, has hampered further characterization of mutp53 DNA binding. Emanating from our previous discovery that DNA structure is an important determinant of wild-type p53 (wtp53) DNA binding, we analyzed the binding of various mutp53 proteins to oligonucleotides mimicking non-B DNA structures. Using various DNA-binding assays we show that mutp53 proteins bind selectively and with high affinity to non-B DNA. In contrast to sequence-specific and DNA structure-dependent binding of wtp53, mutp53 DNA binding to non-B DNA is solely dependent on the stereo-specific configuration of the DNA, and not on DNA sequence. We propose that DNA structure-selective binding of mutp53 proteins is the basis for the well-documented interaction of mutp53 with MAR elements and for transcriptional activities mediates by mutp53.
Correspondence may also be addressed to Ella Kim. Tel: +49 (0)451500 6722; Fax: +49 (0)451500 6191; Email: ella.kim{at}neurochirurgie.uni-luebeck.de
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