Modeling the early stage of DNA sequence recognition within RecA nucleoprotein filaments
Identifieur interne : 003704 ( Main/Merge ); précédent : 003703; suivant : 003705Modeling the early stage of DNA sequence recognition within RecA nucleoprotein filaments
Auteurs : Adrien Saladin [France] ; Christopher Amourda [France] ; Pierre Poulain [France] ; Nicolas Férey [France] ; Marc Baaden [France] ; Martin Zacharias [Allemagne] ; Olivier Delalande [France] ; Chantal Prévost [France]Source :
- Nucleic Acids Research [ 0305-1048 ] ; 2010.
Abstract
Homologous recombination is a fundamental process enabling the repair of double-strand breaks with a high degree of fidelity. In prokaryotes, it is carried out by RecA nucleofilaments formed on single-stranded DNA (ssDNA). These filaments incorporate genomic sequences that are homologous to the ssDNA and exchange the homologous strands. Due to the highly dynamic character of this process and its rapid propagation along the filament, the sequence recognition and strand exchange mechanism remains unknown at the structural level. The recently published structure of the RecA/DNA filament active for recombination (Chen
Url:
DOI: 10.1093/nar/gkq459
PubMed: 20507912
PubMed Central: 2965220
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<series><title level="j">Nucleic Acids Research</title>
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<front><div type="abstract" xml:lang="en"><p>Homologous recombination is a fundamental process enabling the repair of double-strand breaks with a high degree of fidelity. In prokaryotes, it is carried out by RecA nucleofilaments formed on single-stranded DNA (ssDNA). These filaments incorporate genomic sequences that are homologous to the ssDNA and exchange the homologous strands. Due to the highly dynamic character of this process and its rapid propagation along the filament, the sequence recognition and strand exchange mechanism remains unknown at the structural level. The recently published structure of the RecA/DNA filament active for recombination (Chen <italic>et al.</italic>
, Mechanism of homologous recombination from the RecA-ssDNA/dsDNA structure, Nature 2008, 453, 489) provides a starting point for new exploration of the system. Here, we investigate the possible geometries of association of the early encounter complex between RecA/ssDNA filament and double-stranded DNA (dsDNA). Due to the huge size of the system and its dense packing, we use a reduced representation for protein and DNA together with state-of-the-art molecular modeling methods, including systematic docking and virtual reality simulations. The results indicate that it is possible for the double-stranded DNA to access the RecA-bound ssDNA while initially retaining its Watson–Crick pairing. They emphasize the importance of RecA L2 loop mobility for both recognition and strand exchange.</p>
</div>
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