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p53 searches on DNA by rotation-uncoupled sliding at C-terminal tails and restricted hopping of core domains.
MedLine Citation:
PMID:  22880817     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The tumor suppressor p53 is a transcription factor that searches its cognate sites on DNA. During the search, the roles and interplay of its two DNA binding domains, the folded core domain and the disordered C-terminal domain (CTD), have been controversial. Here, we performed molecular simulations of p53 at various salt concentrations finding that, at physiological salt concentration, p53 diffuses along non-specific DNA via rotation-uncoupled sliding with its CTD whereas the core domain repeats dissociation and association. This is in perfect agreement with a recent single molecule experiment. In the simulation of tetrameric full-length p53, two DNA binding domains both bound to non-specific DNA in a characteristic form at low salt concentration, whereas at physiological salt concentration, only CTD kept bound to DNA and the core domain frequently hopped on DNA. Simulations of a construct that lacks the core domain (TetCD) clarified rotation-uncoupled diffusion on non-specific DNA. At low salt concentration, the diffusion constant due to sliding was dependent on the salt concentration, which differs from the prediction of a classic theory of transcription factors. At physiological salt concentration, it was independent of the salt concentration, in harmony with experi-ments. Moreover, we found that the sliding via the CTD follows the helical pitch of DNA (i.e., rotation-coupled sliding) at low salt concentration while it is virtually uncoupled to the helical pitch, a hallmark of rotation-uncoupled sliding at physiological salt concentration.
Authors:
Tsuyoshi Terakawa; Hiroo Kenzaki; Shoji Takada
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-10
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  -     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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