Selective binding of tumor suppressor p53 protein to topologically constrained DNA: Modulation by intercalative drugs
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
20175992
DOI
10.1016/j.bbrc.2010.02.120
PII: S0006-291X(10)00354-2
Knihovny.cz E-zdroje
- MeSH
- akridiny chemie farmakologie MeSH
- chlorochin chemie farmakologie MeSH
- doxorubicin chemie farmakologie MeSH
- interkalátory chemie farmakologie MeSH
- kompetitivní vazba MeSH
- konformace nukleové kyseliny účinky léků MeSH
- lidé MeSH
- nádorový supresorový protein p53 chemie metabolismus MeSH
- superhelikální DNA chemie účinky léků metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- akridiny MeSH
- chlorochin MeSH
- doxorubicin MeSH
- interkalátory MeSH
- nádorový supresorový protein p53 MeSH
- superhelikální DNA MeSH
Selective binding of the wild type tumor suppressor protein p53 to negatively and positively supercoiled (sc) DNA was studied using intercalative drugs chloroquine (CQ), ethidium bromide, acridine derivatives and doxorubicin as a modulators of the level of DNA supercoiling. The p53 was found to lose gradually its preferential binding to negatively scDNA with increasing concentrations of intercalators until the DNA negative superhelix turns were relaxed. Formation of positive superhelices (due to further increasing intercalator concentrations) rendered the circular duplex DNA to be preferentially bound by the p53 again. CQ at concentrations modulating the closed circular DNA topology did not prevent the p53 from recognizing a specific target sequence within topologically unconstrained linear DNA. Experiments with DNA topoisomer distributions differing in their superhelix densities revealed the p53 to bind selectively DNA molecules possessing higher number of negative or positive superturns. Possible modes of the p53 binding to the negatively or positively supercoiled DNA and tentative biological consequences are discussed.
Citace poskytuje Crossref.org
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Preferential binding of hot spot mutant p53 proteins to supercoiled DNA in vitro and in cells