Preferential Binding of Hot Spot Mutant p53 Proteins to Supercoiled DNA In Vitro and in Cells

0392686 - BFÚ 2014 RIV US eng J - Journal Article
Brázdová, Marie - Navrátilová, Lucie - Tichý, Vlastimil - Němcová, Kateřina - Lexa, M. - Hrstka, R. - Pečinka, Petr - Adámik, Matěj - Vojtěšek, B. - Paleček, Emil - Deppert, W. - Fojta, Miroslav
Preferential Binding of Hot Spot Mutant p53 Proteins to Supercoiled DNA In Vitro and in Cells.
PLoS ONE. Roč. 8, č. 3 (2013), e59567. ISSN 1932-6203. E-ISSN 1932-6203
R&D Projects: GA ČR(CZ) GAP301/10/2370; GA ČR GA13-36108S; GA ČR(CZ) GP204/06/P369; GA ČR(CZ) GA204/08/1560; GA ČR(CZ) GAP301/11/2055; GA MŠMT(CZ) 1K04119
Grant - others:GA ČR(CZ) GAP301/11/1678
Institutional research plan: CEZ:AV0Z50040702
Keywords : TUMOR-SUPPRESSOR P53 * C-TERMINAL DOMAIN * OF-FUNCTION MUTATIONS
Subject RIV: BO - Biophysics
Impact factor: 3.534, year: 2013

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 wildtype p53 to preferentially bind circular DNA at native negative superhelix density, while linear or relaxed circular DNA was a poor substrate.
Permanent Link: http://hdl.handle.net/11104/0221502