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@article{1163356,
author = {Brázdová, Marie and Navratilova, Lucie and Tichý, Vlastimil and Němcová, Kateřina and Lexa, Matej and Hrstka, Roman and Pecinka, Petr and Adámik, Matej and Vojtěšek, Bořivoj and Palecek, Emil and Deppert, Wolfgang and Fojta, Miroslav},
article_location = {SAN FRANCISCO},
article_number = {3},
doi = {http://dx.doi.org/10.1371/journal.pone.0059567},
keywords = {p53 tumor supressor; mutp53 oncogenic mutations; DNA topology; superhelicity; DNA binding; BAX MSP/MST1 promoter},
language = {eng},
issn = {1932-6203},
journal = {Plos One},
title = {Preferential Binding of Hot Spot Mutant p53 Proteins to Supercoiled DNA In Vitro and in Cells},
url = {http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0059567},
volume = {8},
year = {2013}
}
TY - JOUR
ID - 1163356
AU - Brázdová, Marie - Navratilova, Lucie - Tichý, Vlastimil - Němcová, Kateřina - Lexa, Matej - Hrstka, Roman - Pecinka, Petr - Adámik, Matej - Vojtěšek, Bořivoj - Palecek, Emil - Deppert, Wolfgang - Fojta, Miroslav
PY - 2013
TI - Preferential Binding of Hot Spot Mutant p53 Proteins to Supercoiled DNA In Vitro and in Cells
JF - Plos One
VL - 8
IS - 3
SP - "e59567"
EP - "e59567"
PB - PUBLIC LIBRARY SCIENCE
SN - 19326203
KW - p53 tumor supressor
KW - mutp53 oncogenic mutations
KW - DNA topology
KW - superhelicity
KW - DNA binding
KW - BAX MSP/MST1 promoter
UR - http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0059567
L2 - http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0059567
N2 - Hot spot mutant p53 (mutp53) proteins exert oncogenic gain-of-function activities. Binding of mutp53 to DNA is assumed to be involved in mutp53-mediated repression or activation of several mutp53 target genes. To investigate the importance of DNA topology on mutp53-DNA recognition in vitro and in cells, we analyzed the interaction of seven hot spot mutp53 proteins with topologically different DNA substrates (supercoiled, linear and relaxed) containing and/or lacking mutp53 binding sites (mutp53BS) using a variety of electrophoresis and immunoprecipitation based techniques. All seven hot spot mutp53 proteins (R175H, G245S, R248W, R249S, R273C, R273H and R282W) were found to have retained the ability of wild-type p53 to preferentially bind circular DNA at native negative superhelix density, while linear or relaxed circular DNA was a poor substrate. The preference of mutp53 proteins for supercoiled DNA (supercoil-selective binding) was further substantiated by competition experiments with linear DNA or relaxed DNA in vitro and ex vivo. Using chromatin immunoprecipitation, the preferential binding of mutp53 to a sc mutp53BS was detected also in cells. Furthermore, we have shown by luciferase reporter assay that the DNA topology influences p53 regulation of BAX and MSP/MST1 promoters. Possible modes of mutp53 binding to topologically constrained DNA substrates and their biological consequences are discussed.
ER -
BRÁZDOVÁ, Marie, Lucie NAVRATILOVA, Vlastimil TICHÝ, Kateřina NĚMCOVÁ, Matej LEXA, Roman HRSTKA, Petr PECINKA, Matej ADÁMIK, Bořivoj VOJTĚŠEK, Emil PALECEK, Wolfgang DEPPERT and Miroslav FOJTA. Preferential Binding of Hot Spot Mutant p53 Proteins to Supercoiled DNA In Vitro and in Cells. \textit{Plos One}. SAN FRANCISCO: PUBLIC LIBRARY SCIENCE, 2013, vol.~8, No~3, p.~''e59567'', 17 pp. ISSN~1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0059567.
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