Document Detail


Targeting human Rad51 by specific DNA aptamers induces inhibition of homologous recombination.
MedLine Citation:
PMID:  20713120     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Human Rad51 (HsRad51), a key element of the homologous recombination repair pathway, is related to the resistance of cancer cells to chemo- and radio-therapies. This protein is thus a good target for the development of anti-cancer treatments. We have searched for new inhibitors directed against HsRad51 using the Systematic Evolution of Ligands by EXponential enrichment (SELEX) approach. We have selected three aptamers displaying strong effects on strand exchange activity. Analysis by circular dichroism shows that they are highly structured DNA molecules. Our results also show that they affect the first step of the strand exchange reaction by promoting the dissociation of DNA from the ATP/HsRad51/DNA complex. Moreover, these inhibitors bind only weakly to RecA, a prokaryotic ortholog of HsRad51. Both the specificity and the efficiency of their inhibition of recombinase activity offer an analytical tool based on molecular recognition and the prospect of developing new therapeutic agents.
Authors:
Susan F Martinez; Axelle Renodon-Cornière; Julian Nomme; Damien Eveillard; Fabrice Fleury; Masayuki Takahashi; Pierre Weigel
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-14
Journal Detail:
Title:  Biochimie     Volume:  92     ISSN:  1638-6183     ISO Abbreviation:  Biochimie     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1264604     Medline TA:  Biochimie     Country:  France    
Other Details:
Languages:  eng     Pagination:  1832-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Masson SAS. All rights reserved.
Affiliation:
UMR 6204, Centre National de la Recherche Scientifique & Université de Nantes, 44322 Nantes cedex 3, France.
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