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Nucleic Acids Res. 2019 Sep 5;47(15):7798-7808. doi: 10.1093/nar/gkz667.

Weaving DNA strands: structural insight on ATP hydrolysis in RecA-induced homologous recombination.

Author information

1
CNRS, Université de Paris, UPR 9080, Laboratoire de Biochimie Théorique, 13 rue Pierre et Marie Curie, F-75005 Paris, France.
2
Presently in Laboratoire Génomique Bioinformatique et Applications, EA4627, Conservatoire National des Arts et Métiers, 292 rue Saint Martin, 75003 Paris, France.
3
Department of Physics, Harvard University, Cambridge, MA 02138, USA.
4
Institut de Biologie Physico-Chimique-Fondation Edmond de Rothschild, PSL Research University, Paris, France.

Abstract

Homologous recombination is a fundamental process in all living organisms that allows the faithful repair of DNA double strand breaks, through the exchange of DNA strands between homologous regions of the genome. Results of three decades of investigation and recent fruitful observations have unveiled key elements of the reaction mechanism, which proceeds along nucleofilaments of recombinase proteins of the RecA family. Yet, one essential aspect of homologous recombination has largely been overlooked when deciphering the mechanism: while ATP is hydrolyzed in large quantity during the process, how exactly hydrolysis influences the DNA strand exchange reaction at the structural level remains to be elucidated. In this study, we build on a previous geometrical approach that studied the RecA filament variability without bound DNA to examine the putative implication of ATP hydrolysis on the structure, position, and interactions of up to three DNA strands within the RecA nucleofilament. Simulation results on modeled intermediates in the ATP cycle bring important clues about how local distortions in the DNA strand geometries resulting from ATP hydrolysis can aid sequence recognition by promoting local melting of already formed DNA heteroduplex and transient reverse strand exchange in a weaving type of mechanism.

PMID:
31372639
PMCID:
PMC6735932
DOI:
10.1093/nar/gkz667
[Indexed for MEDLINE]
Free PMC Article

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