Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Structral insights into the mechanism of homologous recombination

The recognition and strand exchange process central to homologous recombination (HR) involves structural transitions for both the DNA and the protein filament components. The DNA engaged in the HR process goes from a B-DNA form outside the recombinase filament to a stretched/unwound form when incorporated within that filament. This transition has long been thought to be a key issue for the HR mechanism. Based on the comparison with known protein-DNA complexes where the protein locally induces distortions of the same type, and on new modeling studies including docking exploration and molecular dynamics simulation, we propose a sequence of mechanical events involving DNA structural transitions that results in locally destabilizing the DNA base pairing and inducing pairing exchange, at the heart of the HR process. Our modeling strategy explicitly considered the intrinsically multiscale character of the HR reaction by integrating physical models of homologous search into detailed structural and functional features of the system. This strategy and its importance to elucidating a mechanism characterized by dynamic evolution both in time and space will be discussed in the light of previously published information on the system. Finally, the recombinase filament itself can change the internal arrangement of its monomers upon ATP hydrolysis, which modifies its helical form. Insight on these transitions, and their possible connection to the proposed HR mechanism, will be discussed. This research has been supported by NSF Research Fellowship Grant No. DGE-1144152; IDEX DYNAMO Grant ANR-11-LABX-0011-01. The work used the computer resources of Stampede at the Texas Advanced Computing Center (TACC) under an XSEDE startup allocation (TG-MCB130076).


    C. Prevost & Takahashi, M. (2004) Geometry of the DNA strands within the RecA nucleofilament: role in homologous recombination. Q Rev Biophys, 36, 429-453

    B. Boyer, Ezelin, J., Poulain, P. , Saladin, A., Zacharias, M., Robert, C. H. & Prevost, C. (2015) An integrative approach to the study of filamentous oligomeric assemblies, with application to RecA. PloS ONE, in press

    D. Yang, B. Boyer, C. Prevost, C. Danilowicz, and M. Prentiss. Integrating Multi-Scale Data on Homologous Recombination into a New Recognition Mechanism based on Simulations of the RecA-ssDNA/dsDNA Structure. to be submitted

Benjamin Boyer 1
Darren Yang2
Claudia Danilowicz3
Mara Prentiss3
Chantal Prevost1

1LBT, CNRS, Univ Paris Diderot
Sorbonne Paris Cite
Paris, France
2School of Engineering and Applied Sciences
Harvard University
Cambridge, USA
3Department of Physics
Harvard University
Cambridge, USA

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