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Two distinct conformational states define the interaction of human RAD51‐ATP with single‐stranded DNA

Abstract : An essential mechanism for repairing DNA double-strand breaks is homologous recombination (HR). One of its core catalysts is human RAD51 (hRAD51), which assembles as a helical nucleoprotein filament on single-stranded DNA, promoting DNA-strand exchange. Here, we study the interaction of hRAD51 with single-stranded DNA using a single-molecule approach. We show that ATP-bound hRAD51 filaments can exist in two different states with different contour lengths and with a free-energy difference of~4 k B T per hRAD51 monomer. Upon ATP hydrolysis, the filaments convert into a disassembly-competent ADP-bound configuration. In agreement with the single-molecule analysis, we demonstrate the presence of two distinct protomer interfaces in the crystal structure of a hRAD51-ATP filament, providing a structural basis for the two conformational states of the filament. Together, our findings provide evidence that hRAD51-ATP filaments can exist in two inter-convertible conformational states, which might be functionally relevant for DNA homology recognition and strand exchange.
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Submitted on : Tuesday, November 26, 2019 - 12:09:10 PM
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Ineke Brouwer, Tommaso Moschetti, Andrea Candelli, Edwige B Garcin, Mauro Modesti, et al.. Two distinct conformational states define the interaction of human RAD51‐ATP with single‐stranded DNA. EMBO Journal, EMBO Press, 2018, 37 (7), ⟨10.15252/embj.201798162⟩. ⟨hal-01789423⟩

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