首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Selective binding of tumor suppressor p53 protein to topologically constrained DNA: Modulation by intercalative drugs
Authors:Hana Pivoňková  Peter Šebest  Olga Tichá  Marie Brázdová  Václav Brázda
Institution:a Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno, Czech Republic
b Faculty of Science, University of Ostrava, 701 03 Ostrava, Czech Republic
Abstract: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.
Keywords:AA  2-amino acridine  cccDNA  covalently closed circular DNA  CQ  chloroquine  DX  doxorubicin  Etd  ethidium bromide  p53CON  p53 consensus sequence  linDNA  linear DNA  pro  proflavine  σ  superhelix density  σ0  superhelix density in absence of intercalator (&ldquo  initial superhelix density&rdquo  )  scDNA  supercoiled DNA  SCS  supercoil-selective  MB  magnetic beads  MBIP  magnetic beads-based immunoprecipitation
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号