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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 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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